Active and total T cells in blood and cerebrospinal fluid during the course of aseptic meningitis

Patients with aseptic meningitis (AM) were examined with the active T cell rosette test, which has been claimed to reflect cell-mediated immunocompetence more accurately than determination of total T cells. Higher percentages of active T cells were demonstrated in CSF compared to blood regardless if specimens were obtained on days 1–4, days 5–10, or later than 20 days after onset of symptoms. Active T cell percentages in CSF decreased when values for specimens obtained on days 5–10 were compared with those taken later than 20 days after onset, while no significant variations of active T cell percentages in blood were observed. The percentages of total T cells were higher in CSF than blood in specimens from days 5–10, and later than 20 days after onset, but no significant fluctuations of total T cells occurred in either CSF or blood over the course of AM.     

Immunoglobulins in serum and cerebrospinal fluid from patients with acute Guillain-Barré syndrome

IgG, IgA, IgM and IgE were quantified in serum and IgG and total protein were quantified in cerebrospinal fluid (CSF) from 80 patients with acute Guillain-Barré syndrome. The serum concentrations of IgM and IgA were significantly increased in approximately 25% of the patients, whereas the concentrations of IgG and IgE were normal. Increased CSF concentrations of IgG were found in more than 90% of the patients and correlated with increased CSF total protein concentrations. The CSF IgG/total protein ratio, CSF IgG index and Tourtellotte's formula were used to determine intra-thecal IgG synthesis in 30 of the patients. In eight of the patients the results of the CSF IgG index and Tourtellotte's formula were significantly increased, while in the remaining seven patients increased values were obtained using only one of these formulae. The CSF IgG/total protein ratio was normal in all the patients. Oligoclonal bands were not detected in any of the sera or CSF. Antibodies to peripheral nerve tissue were detected in approximately 30% of the patient sera, but could not be detected in the CSF.     

Prognostic value of cerebrospinal fluid neuron-specific enolase and S-100b protein in Guillain-Barré syndrome

We measured the cerebrospinal fluid (CSF) concentrations of neuron-specific enolase (NSE) and S-100b protein (S-100b) using enzyme immunoassay methods, in 24 patients with Guillain-Barré syndrome and 46 controls, and examined their prognostic values. Sixteen of 24 patients showed elevated levels (> the mean + 2SD levels of controls) of NSE, S-100b, or both, and in those with higher NSE or S-100b levels there was a rather longer duration of disease, whereas 8 patients with the normal levels showed an early recovery. Further, NSE or S-100b levels were significantly correlated with months to recovery. Thus, NSE and S-100b in CSF may be useful markers for predicting the outcome of Guillain-Barré syndrome.     

Guillain–Barré syndrome with marked pleocytosis or a significant proportion of polymorphonuclear granulocytes in the cerebrospinal fluid: neuropathological investigation of five cases and review of differential diagnoses

In cases with otherwise clinically typical Guillain-Barré syndrome (GBS), pronounced cerebrospinal fluid (CSF) pleocytosis or the mere presence of CSF-polymorphonuclear granulocytes should alert the physician to consider alternative diagnoses. Therefore, we retrospectively studied the neuropathology of central and peripheral nervous system in two cases with a CSF cell count of more than 50/microl and in three cases with a significant proportion of polymorphonuclear granulocytes in the CSF sediment. All cases fulfilled the required criteria for the diagnosis of GBS, the duration from onset to death ranged from 4 to 100 days. Neuropathological investigations included routine staining procedures and immunohistochemistry for antigens of glial and haematopoetic cells as well as for products of relevant neurotropic viruses. Demyelinating polyradiculitis was present in four cases, in one patient with a survival time of 4 days the type of damage to myelinated fibres was unclassifiable. In the central nervous system a consistent finding was diffuse activation of microglia, only one case showed mild meningeal and lower brainstem inflammation. Viral products were generally absent. In summary, the neuropathological findings confirm that marked CSF pleocytosis or the presence of polymorphonuclear granulocytes does not rule out the diagnosis of GBS.     

神经白塞综合征的临床和脑脊液细胞学特点

目的回顾性分析神经白塞综合征(NBS)临床和脑脊液(CSF)细胞学资料,探讨该病的临床和CSF细胞学特点。方法回顾1991-2010年间北京协和医院NBS住院患者共27例,分析其临床表现、神经影像学和CSF细胞学特点。结果 27例患者中,神经科症状急性病程19例,亚急性病程6例,慢性病程2例。临床表现:头痛9例,偏瘫8例,复视6例,偏身感觉障碍5例,意识障碍5例,失语3例,癫痫发作3例,精神行为异常、智能减退6例,截瘫2例,共济失调2例,呛咳、吞咽困难2例,帕金森综合征1例。头MRI异常16例,多发片状T1低或较低信号,T2高信号,病灶分布于基底节、脑干、丘脑等处,9例行增强MRI均有强化;2例颈段脊髓MRI可见强化病灶。磁共振静脉成像(MRV):1例符合上矢状窦血栓形成。CSF检查:19例行腰穿查CSF,其中8例压力升高,17例蛋白升高(0.48～1.08g/L);行CSF细胞学检查(沉淀池法制片,迈-格-姬染色)的11例中7例表现为淋巴细胞为主的炎性反应,其中6例伴有中性粒细胞比例升高,余4例中3例为淋巴细胞与中性粒细胞为主的混合性炎性反应,1例为中性粒细胞性炎性反应,8例可见激活淋巴细胞,4例可见浆细胞。结论 NBS临床表现多样,神经影像学改变以基底节、脑干和丘脑等邻近中线的结构受累为主,CSF细胞学呈炎性反应表现。CSF细胞学炎性反应类型,特别是CSF中性粒细胞比例升高对NBS的诊断具有一定意义。     

CSF lymphocyte subsets in aseptic meningitis: dual-labelling analysis with flow cytometry

In order to characterize the CSF (cerebrospinal fluid) lymphocytes in CNS (central nervous system) inflammation, we examined paired samples of CSF and PB (peripheral blood) of 19 patients with acute aseptic meningitis, performing the dual labelling method on flow cytometry. Significantly higher percentages of CD3+ (T cell), CD4+ (helper-inducer), Leu3a+ Leu15- (cytotoxic-T) and HLA-DR+ CD3+ (activated-T) cells were identified in the CSF than in the PB of these patients. We observed significantly lower percentages of CD19+ (B cell), Leu2a+ Leu18+ (suppressor-inducer) and HLA-DR+ CD3- cells in the CSF than in the PB of these patients. Relative increases in helper-inducer, cytotoxic-T and activated-T cells in the CSF of aseptic meningitis are supposed to represent an active inflammatory process. However, whether these changes are specific or pathognomonic to any disease(s) remains to be solved.     

老年患者结核性脑膜炎脑脊液细胞学及临床特点

目的探讨老年结核性脑膜炎患者脑脊液细胞学(CSF)变化及临床特点。方法42例病人经临床和辅助检查确诊,采用脑脊液细胞玻片离心沉淀法收集细胞,经MGG染色后在显微镜下观察。结果全部病例脑脊液细胞学均有异常,老年患者脑脊液细胞学有明显不同的特点。结论初诊时,脑脊液细胞学以淋巴细胞比例占优势较多,随病程进展出现程度不同的混合细胞反应,治疗有效者嗜中性粒细胞下降及消失较快;一部分患者一直以淋巴细胞占优势,伴有激活淋巴细胞、激活单核细胞,并持续性较长时间。脑脊液细胞学的动态变化,为判断老年结核性脑膜炎的病情转归、疗效有着重要的临床价值。     

The olfactory route for cerebrospinal fluid drainage into the peripheral lymphatic system

Drainage of the cerebrospinal fluid through the olfactory nerves into the nasal lymphatics has been suggested repeatedly. To investigate precisely the morphology of this pathway, India ink was injected into the subarachnoidal space of the rat brain, and samples including the olfactory bulbs, olfactory tracts and the nasal mucosa were observed by light and electron microscopy. Under the dissecting microscope, ink particles were found within the subarachnoid space and along the olfactory nerves. At the nasal mucosa, a lymphatic network stained in black was identified near the olfactory nerves, which finally emptied into the superficial and deep cervical lymph nodes. Light microscopically, ink particles were found in the subarachnoid space, partially distributed around the olfactory nerves and within the lymphatic vessels. By electron microscopy, the subarachnoid space often formed a pocket-like space in the entrance of the fila olfactoria. The olfactory nerves were partially surrounded by ink particles within the space between perineurial cells and epineurial fibroblasts. At the nasal mucosa, the lymphatics were frequently located close to the nerves. These results indicate that the cerebrospinal fluid drains from the subarachnoid space along the olfactory nerves to the nasal lymphatics, which in turn, empties into the cervical lymph nodes. This anatomical communication, thus, allows the central nervous system to connect with the lymphatic system. The presence of this route may play an important role in the movement of antigens from the subarachnoidal space to the extracranial lymphatic vessels, resulting in inducement of an immune response of the central nervous system.     

Plasma exchange in Guillain-Barré syndrome: effect on anti-peripheral nerve myelin antibodies

Increased levels of anti-peripheral nerve myelin (anti-PNM) antibodies were demonstrated by ELISA in serum from 4 of 7 patients with Guillain-Barré syndrome (GBS). Treatment with plasma exchange (PE) was performed and 6 of the 7 patients showed clinical improvement with marked increase in muscular strength. One patient, however, continued to deteriorate during the treatment. No correlation between clinical improvement and levels of anti-PNM antibodies was observed. Whether the antibodies are of pathogenetic importance in GBS is therefore still unknown.     

T-cell subsets in multiple sclerosis: relationships between peripheral blood and cerebrospinal fluid

We contemporarily studied cerebrospinal fluid (CSF) and peripheral blood (PB) T-cell subsets, defined by monoclonal antibodies, in 29 patients with multiple sclerosis (MS) and 10 patients with other neurological diseases (OND). All subjects showed a clear-cut prevalence of CSF T-cells. Similarly, T-helper and T-suppressor subsets tended to show higher percentages in CSF in almost all subjects except relapsing MS, who were characterized by low percentages of T-suppressors in PB and even much lower percentages in CSF. Helper/suppressor ratios were found to be almost similar in the two body compartments of OND patients, lower in CSF than in PB of chronic progressive MS, always higher in CSF than in PB of relapsing MS. MS patients in remission showed both patterns of progressive MS and OND patients. Our results demonstrate that the loss of PB T-suppressor in relapsing MS is not due to a migration of such cells into CSF. Furthermore, regarding T-lymphocyte subsets, a typical CSF/PB pattern characterizes relapsing MS from other patients.     

Newest human herpesvirus (HHV-6) in the Guillain-Barré syndrome and other neurological diseases

To investigate the presence of human herpesvirus-6 (HHV-6) in patients affected by Guillain-Barré syndrome (GBS) and by other neurological diseases (OND), we examined by indirect immunofluorescence analysis (IFA) the sera and cerebrospinal fluid (CSF) from 28 GBS and 63 OND. Moreover, we tested 150 blood donors (BD) to appreciate the diffusion of HHV-6 infection in the Italian adult healthy population. We found a significantly higher titre of antibody to HHV-6 in the GBS patients compared with OND and BD, although the pathogenicity of the virus is not known.     

Analysis of lymphocyte subpopulations in cerebrospinal fluid and peripheral blood in patients with multiple sclerosis and inflammatory diseases of the nervous system

We analysed different subsets of lymphocytes from peripheral blood (PB) and cerebrospinal fluid (CSF) by flow cytometry in order to determinate alterations in patients with multiple sclerosis (MS) in acute relapse and viral inflammatory neurological disease (IND). We found increased levels of adhesion molecules (LFA-1 and β₁ integrin) in the CSF of patients with MS and IND compared to NIND. CD4 ⁺/CD8 ⁺ ratio was significantly higher in CSF of MS as compared with all groups analysed and compared with PB. We detected a significantly higher expression of the interleukin-2 receptor in PB of MS patients when compared with other groups. In patients with IND a significant higher expression of the interleukin-2 receptor was found in the CSF compared with MS and NIND. Our findings indicate that the activation of T lymphocytes primarily occurs in the peripheral immune compartment in MS and the increase of adhesion molecules in CSF is related to inflammatory disorders and not only to MS.     

Olfactory route for cerebrospinal fluid drainage into the cervical lymphatic system in a rabbit experimental model

The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil (Microfil compounds fill and opacify microvascular and other spaces of non-surviving animals and post-mortem tissue under physiological injection pressure) were injected into the cisterna magna of the rabbit, and perineural routes of cerebrospinal fluid outflow into the lymphatic system were visualized. Under a surgical operating microscope, Microfil was found within the subarachnoid space and along the olfactory nerves. At the nasal mucosa, a lymphatic network was identified near the olfactory nerves, which crossed the nasopharyngeal region and finally emptied into the superficial and deep cervical lymph nodes. Under a light microscope, Microfil was visible around the olfactory nerves and within lymphatic vessels. These results suggested that cerebrospinal fluid drained from the subarachnoid space along the olfactory nerves to nasal lymphatic vessels, which in turn, emptied into the cervical lymph nodes. This anatomical route, therefore, allowed connection between the central nervous system and the lymphatic system.     

回顾性分析成人化脓性脑膜炎细菌构成及其脑脊液分布特点

目的回顾性分析宁夏地区成人化脓性脑膜炎(purulent meningitis in adult,APM)患者脑脊液(cerebrospinal Fluid,CSF)细菌构成及特点。方法收集宁夏医科大学总医院2002年01月至2014年07月诊治并行细菌培养的144例化脓性脑膜炎患者临床资料,分析比较致病菌检出阳性与阴性的实验室检查特点,以及不同致病菌(革兰阳性球菌、革兰阴性杆菌及革兰阳性杆菌)患者之间实验室检查特点。结果 144例化脓性脑膜炎的细菌检出阳性率为36.8%(53例),致病细菌以革兰阳性球菌常见[64.15%(34例)],其中以葡萄球菌属为主;细菌检出阳性组患者的血中性粒细胞比例、脑脊液白细胞计数及脑脊液蛋白含量均高于阴性组(分别(82.52±9.43)%,(78.13±13.25)%,P=0.022;(4078.13±5739.24)×10~6/L,(2181.61±4440.87)×10~6/L,P=0.010;(2.99±2.67)g/L,(2.18±2.01)g/L,P=0.041)。发病10d内就诊的101例患者,细菌检出阳性组脑脊液压力、脑脊液白细胞计数、脑脊液中性粒细胞比例亦均高于阴性组((263.82±55.05)mmH_2O,(236.03±66.26)mmH_2O,P=0.032;(4660.45±5756.37)×10~6/L,(2745.97±5193.33)×106/L,P=0.008;(70.21±30.51)%,(56.79±35.54)%,P=0.048),脑脊液淋巴细胞比例较阴性组低((18.92±24.10)%,(32.02±32.10)%,P=0.023)。结论成人化脓性脑膜炎的致病菌以革兰阳性球菌多见,其细菌培养阳性患者的脑脊液与培养阴性者具有一定差异,可能会为临床诊疗提供参考价值。     

Clinical and cerebrospinal fluid findings in lymphocytic meningo-radiculitis (Bannwarth's syndrome)

11 patients with lymphocytic meningo-radiculitis (Bannwarths syndrome) are described. The disease is characterized by intensive pain, often radiating and migrating, and neurological deficits, i.e. peripheral facial palsies, as well as disseminated radiculopathies. In 4 patients the onset was preceeded by an arthropode bite, close to which 3 patients exhibited an erythema chronicum migrans.
In the cerebrospinal fluid there was a mononuclear pleocytosis, predominately by lymphocytes. In the early stages, a plasma cell reaction was frequently encountered. Protein analysis indicated a defect in the blood brain barrier and an intrathecal synthesis of IgG.
All patients recovered almost completely from their neurological symptoms within 1–2 months, irrespective of treatment.     

Terminal component of complement C9 in CSF and plasma of patients with MS and aseptic meningitis

A sensitive sandwich ELISA was applied to the measurement of the terminal component of complement C9 in CSF and plasma from 40 tension headache patients (reference group), 33 affected by clinically definite MS and 10 by aseptic meningitis. The levels of C9 in plasma were increased in aseptic meningitis. The determinations of CSF/plasma C9 ratio and C9 index, equal to (CSF C9/plasma C9): (CSF albumin/plasma albumin), thus accounting for changes of plasma C9 levels as well as damaged blood brain barrier, documented the existence of local consumption of C9 in aseptic meningitis. In contrast, only borderline alterations were evident in MS. The results indicate that local consumption of total C9 in CSF is an additional variable reflecting an acute inflammation within the CNS, but not demonstrable in MS, a chronic inflammatory CNS disorder.     

脑脊液与血浆的蛋白、糖、氯化物不同比值鉴别诊断结核性脑膜炎与病毒性脑膜炎的意义

目的 研究脑脊液(CSF)与血浆的蛋白、糖、氯化物含量不同比值鉴别诊断结核性脑膜炎(结脑)与病毒性脑膜炎(病脑)的意义.方法 检测102例结脑和107例病脑患者CSF和血浆的蛋白、糖、氯化物含量,计算CSF与血浆的蛋白、糖、氯化物含量3种不同比值(CSF/血浆蛋白≥0.2、糖≤0.5、氯≤0.7,CSF/血浆蛋白≥0.1、糖≤0.6、氯≤1.1,CSF/血浆蛋白≥0.3、糖≤0.4、氯≤0.6)诊断结脑的敏感性和特异性.结果 结脑组CSF与血浆的蛋白、糖、氯化物含量3种比值的阳性率均显著高于病脑组(P<0.05～0.01);以CSF/血浆的蛋白≥0.2、糖≤0.5、氯≤0.7诊断结脑的敏感性(96.1%,97.1%,99.0%)和特异性(97.2%,98.1%,99.1%)均较高,而CSF/血浆的蛋白>10.1、糖≤0.6、氯≤1.1的特异性(66.4%,69.2%,75.7%)较低,CSF/血浆的蛋白≥0.3、糖≤0.4、氯≤0.6的敏感性(48.0%,44.1%,42.2%)较低.结论 CSF与血浆的蛋白、糖、氯化物含量比值≥0.2、≤0.5及≤0.7对鉴别诊断结脑与病脑具有重要意义.