Criteria for the diagnosis of neurosyphilis in cerebrospinal fluid: relationships with intrathecal immunoglobulin synthesis and blood-cerebrospinal fluid barrier dysfunction.

BACKGROUND: The origin of cerebrospinal fluid (CSF) syphilis antibodies (intrathecal or blood-derived) is in doubt. Little is known about CSF test behavior under the condition of physiological or disturbed functioning of blood-CSF barrier (BCB) and intrathecal immunoglobulin (Ig) production. METHODS: We collected 126 serum/CSF pairs from patients with serological evidence of syphilis. We explored the relationships between the established facts of intrathecal Ig synthesis and/or BCB dysfunction and the results of CSF diagnostic tests: the Treponema pallidum hemagglutination (TPHA) test, the fluorescent treponemal antibody absorption (FTA-Abs) test, the Venereal Disease Research Laboratory (VDRL) test, and white blood cell counts. We checked the criteria used either to support or refute the diagnosis of neurosyphilis. RESULTS: Reactive CSF-VDRL tests, elevated CSF-white blood cell counts, and elevated CSF-TPHA titers/indices were associated with the signs of intrathecal Ig synthesis, whereas nonreactive CSF-fluorescent treponemal antibody absorption, nonreactive CSF-TPHA tests, and CSF-TPHA titers from 1:4 to 1:160 were associated with cases where the intrathecal synthesis was not detected. There were some peculiarities of the tests toward BCB dysfunction.Most of reactive CSF-VDRL test samples and CSF samples with pleocytosis were also meeting at least 1 of the CSF-TPHA titer/indices-based criteria. T. pallidum hemagglutination indices were in no better conformity with the facts of intrathecal immune response than CSF-TPHA titers. CONCLUSIONS: Our findings have shown that all the examined criteria for the diagnosis of neurosyphilis in CSF are different assessment tools of intrathecal humoral immune activity and support the hypothesis that high CSF treponemal-specific antibody titers are a consequence of inflammatory pathology of the central nervous system.

Chorea in systematic lupus erythematosus; a case report.

We report a 33-year-old female who developed a movement disorder during maintenance therapy for systemic lupus erythematosus (SLE). She was diagnosed with SLE at the age of 25, and experienced an episode of SLE-associated hemophagocytic syndrome at age 27, which was successfully treated with intensive immunosuppressive therapy. In November 2012, during maintenance therapy with prednisolone (PSL) 5 mg/day and tacrolimus 0.5 mg/day, she developed acute-onset involuntary movements that were classified as chorea in combination with athetosis in her right limbs and right homonymous hemianopia, which subsided after about 1 h. Her laboratory tests on admission showed an elevated serum anti-double- stranded DNA antibody, positive serum anti-cardiolipin IgG, and an elevated IgG index in cerebrospinal fluid. Magnetic resonance imaging (MRI) showed no significant abnormality on admission, but an ischemic change in her left pallidum appeared on day 7. She was treated with a combination of high-dose corticosteroid, immunosuppressive agents (rituximab, cyclophosphamide, mycofenolate mofetil), antithrombotic therapy (heparin, cilostazol), and dopamine antagonists. Her symptoms remitted partially. Chorea in SLE is recognized as an anti-phospholipid-antibody-associated disorder. In our case, both immunological and ischemic mechanisms were thought to be involved.

Detection of antiphospholipid antibody in children with Henoch-Schönlein purpura and central nervous system involvement.

To explore the mechanisms of central nervous system involvement in children with Henoch-Schönlein purpura, levels of lupus anticoagulant, anticardiolipin antibodies, and anti-ß2 glycoprotein I antibodies in serum and cerebrospinal fluid were determined in 46 cases of Henoch-Schönlein purpura with central nervous system involvement. Results indicated that Henoch-Schönlein purpura with central nervous system involvement produced a higher total percentage of antiphospholipid antibodies in serum and cerebrospinal fluid, compared with viral encephalitis control subjects (76.1% vs 10.0% and 71.7% vs 0.0%, respectively; P < 0.05). Henoch-Schönlein purpura may be associated with antiphospholipid syndrome or antiphospholipid antibodies, which may account for the neurologic damage in Henoch-Schönlein purpura.

A comparative audit of anticardiolipin antibodies in oligoclonal band negative and positive multiple sclerosis.

It has been suggested that multiple sclerosis (MS) patients with positive anticardiolipin antibodies (ACLA) have some atypical features, including absent oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). Our aim was to compare the frequencies of ACLA and related laboratory and clinical features in OCB negative (OCB-) and positive (OCB+) MS patients. We compared 41 OCB- patients attending a MS Clinic in a tertiary referral center, with 206 OCB+ patients. ACLA, anti-beta2-glycoprotein and other autoantibodies, lupus anticoagulant and coagulation markers were measured. We found a higher frequency of ACLA in OCB- patients, 18/41 versus 33/206 in OCB+ patients (P<0.0001). OCB- patients had more progressive MS than OCB+ subjects. There were no differences in age, sex, Expanded Disability Status Scale (EDSS) score, antiphospholipid syndrome symptoms between the groups. ACLA+ MS patients were more frequently in the OCB- group. Although this may suggest that they represent a special subgroup of MS, no other clinical or laboratory findings distinguish the groups. Although OCB- MS patients may be thought to be less active immunologically, this study shows they have more frequently ACLA than OCB+ patients. OCB- MS patients in our cohort do not appear to have a more benign form of MS, as has previously been suggested.

Autoimmune epilepsy: some epilepsy patients harbor autoantibodies to glutamate receptors and dsDNA on both sides of the blood-brain barrier, which may kill neurons and decrease in brain fluids after hemispherotomy.

PURPOSE: Elucidating the potential contribution of specific autoantibodies (Ab's) to the etiology and/or pathology of some human epilepsies. METHODS: Six epilepsy patients with Rasmussen's encephalitis (RE) and 71 patients with other epilepsies were tested for Ab's to the "B" peptide (amino acids 372-395) of the glutamate/AMPA subtype 3 receptor (GluR3B peptide), double-stranded DNA (dsDNA), and additional autoimmune disease-associated autoantigens, and for the ability of their serum and cerebrospinal-fluid (CSF) to kill neurons. RESULTS: Elevated anti-GluR3B Ab' s were found in serum and CSF of most RE patients, and in serum of 17/71 (24%) patients with other epilepsies. In two RE patients, anti-GluR3B Ab's decreased drastically in CSF following functional-hemispherotomy, in association with seizure cessation and neurological improvement. Serum and CSF of two RE patients, and serum of 12/71 (17%) patients with other epilepsies, contained elevated anti-dsDNA Ab's, the hallmark of systemic-lupus-erythematosus. The sera (but not the CSF) of some RE patients contained also clinically elevated levels of "classical" autoimmune Ab's to glutamic-acid-decarboxylase, cardiolipin, beta2-glycoprotein-I and nuclear-antigens SS-A and RNP-70. Sera and CSF of some RE patients caused substantial death of hippocampal neurons. CONCLUSIONS: Some epilepsy patients harbor Ab's to GluR3 and dsDNA on both sides of the blood-brain barrier, and additional autoimmune Ab's only in serum. Since all these Ab's may be detrimental to the nervous system and/or peripheral organs, we recommend testing for their presence in epilepsy, and silencing their activity in Ab-positive patients.

The heterogeneity of neuropsychiatric systemic lupus erythematosus is reflected in lack of association with cerebrospinal fluid cytokine profiles.

The objective was to study the occurrence of autoantibodies and cytokines in serum and cerebrospinal fluid (CSF) in neuropsychiatric systemic lupus erythematosus (NPSLE). In total, 28 consecutive patients with NPSLE and 16 systemic lupus erythematosus (SLE) patients without neuropsychiatric involvement (non-NPSLE) were studied. IFN-alpha, IL-6, IL-10, soluble terminal complement complex (TCC), anti-ribosomal P protein antibodies (anti-P) and anti-cardiolipin antibodies (aCL) were measured in serum and CSF by immunoassays. Analyses of white blood cell differential count, CSF-albumin/serum-albumin ratio, IgG-index in CSF and isoelectric focusing in serum and CSF were also performed. CSF specimens from 23 healthy individuals were used as controls. IFN-alpha was elevated in the CSF of 5 of 28 NPSLE patients compared to three of 14 among the non-NPSLE patients. IL-6 was elevated in CSF in three of 26 NPSLE patients. Normal concentration of IL-10 was found in CSF in all 27 NPSLE-patients analysed. IFN-alpha in serum was elevated in 18 of 28 NPSLE patients. No distinct clinical phenotype was related to elevated cytokine concentration in serum or CSF. One patient with cerebral involvement complicated by progressive multifocal leukoencephalopathy displayed a very high IFN-alpha concentration in serum. High concentration of TCC was present in CSF from only one patient with systemic vasculitis and focal cerebral symptoms. In conclusion, the results of this study suggest that the diagnostic value of serum and CSF concentrations of IFN-alpha, IL-10, IL-6 and TCC is limited in unselected neuropsychiatric SLE, probably due to the heterogeneity of NPSLE pathogenesis.

Immunoserological changes in the cerebro-spinal fluid and serum in systemic lupus erythematosus patients with demyelinating syndrome and multiple sclerosis.

The aim of the present study was to investigate the role of antinuclear and antiphospholipid antibodies in the pathogenesis of systemic lupus erythematosus (SLE) with demyelinating syndrome and several forms of multiple sclerosis (MS). Paired samples of serum and cerebrospinal fluid (CSF) were investigated using laser nephalometric and enzyme linked immunosorbant assay (ELISA) methods, and the parameters of intrathecal synthesis were calculated. Elevation of the concentrations of antiribosomal P protein antibodies in the CSF and serum, and intrathecal synthesis anticardiolipin (aCL) antibodies were characteristic in all patient groups. The immunoserological changes were more pronounced in the SLE patients. A similar pathogenetic role of antiphospholipid antibodies in central nervous system (CNS) damage in SLE patients with demyelinating syndrome and of MS patients can be assumed.

Evaluation of cerebrospinal fluid for the presense of anticardiolipin antibodies (aCL) in NP-SLE patients.

Many neurological or psychiatric manifestations of SLE (NP-SLE) are related to the presence of anticardiolipin antibodies (aCL) in the patient's sera. The aim of this study was to evaluate the presence of aCL in cerebrospinal fluid (CSF) in SLE patients with NP features. Fifteen SLE patients were studied, all with NP features. CSF was evaluated for intrathecal IgG synthesis, oligoclonal IgG, and blood-brain barrier impairment. Sera and CSF were tested by ELISA for the presence of aCL-IgG and aCL-IgM with and without beta2 glycoprotein (beta2 GPI) cofactor. CSF and sera of 50 low back pain patients served as controls. Six patients were aCL(+) and nine aCL(-). In all patients the general CSF examination was normal. In all patients the value of indices of intrathecal IgG synthesis were normal but oligoclonal protein was present in the CSF of three patients. In none of the patients was the blood-brain barrier impaired. Neither aCL-IgG nor aCL-IgM was detected in the CSF of any NP-SLE patient. Mean levels of aCL in patients without cofactor beta2 GPI and with cofactor were as follows: for IgG class 0.005 and 0.057 OD (negative); for IgM class 0.004 and 0.024 OD (negative). We could not detect aCL in the CSF of patients with NP-SLE, even if sera were positive for aCL.

Evaluation of cerebrospinal anticardiolipin antibodies in lupus patients with neuropsychiatric manifestations.

To evaluate the role of cerebrospinal fluid (CSF) anticardiolipin antibody (aCL) in lupus patients with neuropsychiatric manifestations, paired measurements of aCL, in the serum and CSF, were performed using the ELISA method in lupus patients (n=31) and controls with other medical diseases (n=8). High titers of CSF IgG-aCL were detected in cerebral lupus patients with lupus headache, acute psychosis, cognitive impairment, high cortical dysfunction, and altered consciousness. Intrathecal synthesis, rather than the diffusion of IgG-aCL from serum to compartment of the central nervous system, occurred in these NPLE patients. The binding of aCL to brain components might play a role in the development of neuropsychiatric manifestations in cerebral lupus patients.

[Central nervous system involvement in systemic lupus erythematosus].

OBJECTIVE: To investigate central nervous system (CNS) involvements in systemic lupus erythematosus (SLE) so as to enhance our knowledge in diagnosing and treating CNS involvement of SLE. METHODS: The clinical data of 171 in patients with CNS involvement of SLE in our hospital were retrospectively reviewed. RESULTS: The mean SLE disease duration at onset of CNS involvement was (2.21 +/- 1.87) years and in 163 (95.3%) it was associated with active disease. Cerebral spinal fluid abnormality was seen in 91.4% (138/151) of the patients with CNS involvement of SLE. Among them protein elevation was found in 113, pressure elevation in 69, white cell elevation in 51 and glucose reduction in 6. For the evaluation of CNS involvement of SLE, the sensitivity of cranial CT and MRI was 77.4% and 81.4% respectively (P > 0.50). The positive rate of antiribosomal P in patients with diffuse CNS involvement of SLE was significantly higher than that in patients without CNS involvement (P < 0.01). On the contrary, the positive rate of ACL in focal CNS involvement of SLE was significantly higher than that in diffuse type or in patients without CNS involvement (P < 0.01). The total mortality rate in 171 patients with CNS involvement of SLE was 18.7%. The Mortality rate in the period of 1993 to 1998 (4.0%, 3/75) was significantly lower than that of 1980 to 1992 (30.2%, 29/96), P < 0.01. 24 SLE patients with CNS involvement received intrathecal dexamethasone and methotrexate, 22 cases (91.7%) improved considerably. CONCLUSION: CNS involvement occurs in the early stage of SLE, most of the cases are associated with active disease. Cerebral spinal fluid analysis is the most essential test and cranial imaging serves as a supplementary approach, of which CT is preferred. ACL is associated with focal CNS involvement of SLE while antiribosomal P with diffuse CNS involvement of SLE, suggesting there might be different mechanisms in CNS involvement of SLE. Intrathecal therapy is an useful alternative for patients with CNS involvement of SLE refractory to conventional therapy.

Anticardiolipin antibodies in serum and cerebrospinal fluid from patients with systemic lupus erythematosus.

Anticardiolipin antibodies were studied in serum and cerebrospinal fluid from 32 consecutive patients with systemic lupus erythematosus, admitted for the assessment of neuropsychiatric disease. Ten of the 16 patients with active neuropsychiatric complaints showed positive anticardiolipin antibodies in cerebrospinal fluid, including eight with the simultaneous presence of antibodies in their sera. By contrast, only 2 of the 16 patients with headaches, lacking further data of neurological disease, revealed anticardiolipin antibodies in their cerebrospinal fluid. The assessment of Q-albumin index showed abnormal values in a subset of patients with active neuropsychiatric changes who showed positive cerebrospinal anticardiolipin antibodies, suggesting that an impairment of the blood brain barrier function may lead to a leakage of intrathecal antiphospholipid antibodies from systemic circulation. Additionally, few patients revealed normal Q-albumin values with high IgG-cerebrospinal fluid index suggesting increased intrathecal synthesis of autoantibodies. The study of anticardiolipin antibodies in cerebrospinal fluid was useful to detect active neuropsychiatric disease in systemic lupus erythematosus.

Cerebrovascular and neurological disorders associated with antiphospholipid antibodies in CSF and serum.

Paired serum and cerebrospinal fluid (CSF) samples from 70 patients with inflammatory and non-inflammatory neurological diseases, as well as 10 sera from patients with primary antiphospholipid syndrome (PAS), six of which presented with cerebrovascular ischemic syndromes, were studied for the presence of anticardiolipin antibodies (ACA) of the G and M classes. PAS sera and some selected paired CSF and serum specimens, were also analyzed for the presence of anti-phosphatidylserine (PS) and anti-phosphatidylethanolamine (PE) antibodies. High levels of IgG and IgM ACA were synthesized intrathecally only in patients with neurosyphilis. Patients with other infectious or inflammatory neurological diseases very rarely showed detectable levels of ACA in serum and/or CSF. ACA were found not only in patients with untreated PAS but also in the serum of 3/7 patients with migraine, thus confirming a relationship between ACA and vascular disorders. The search for PS and PE antibodies disclosed that in PAS patients the serum titers of these antibodies mirrored ACA IgG and IgM titers, while they were never found in the CSF.

The study of anticardiolipin antibodies and interleukin-6 in cerebrospinal fluid and blood of Chinese patients with systemic lupus erythematosus and central nervous system involvement.

Anticardiolipin (ACL) antibodies and interleukin-6 (IL-6) in cerebrospinal fluid (CSF) may be involved in the mechanism of lupus patients with central nervous system (CNS) involvement. ACL antibodies of 3 isotypes and IL-6 were measured in paired CSF and serum samples from 14 lupus patients with CNS involvement, 5 lupus patients without CNS involvement and 7 patients with non-inflammatory neurological diseases. ACL antibodies, IgG and IgM isotypes, and IL-6 were significantly increased in CSF from lupus patients with CNS involvement as compared with other 2 groups of patients. Both ACL antibodies and IL-6 decreased after neurological activity subsided. These results suggest increased ACL antibodies and IL-6 in CSF are involved in immune responses within CNS in lupus patients. Quantitation of CSF ACL antibodies may be helpful in evaluating neurological activity of lupus patients with CNS involvement.

Anticardiolipin antibodies and interleukin-6 in cerebrospinal fluid and blood of Chinese patients with neuro-Behçet's syndrome.

Anticardiolipin antibodies of the IgG, IgM and IgA isotypes and soluble IL-6 were measured in paired serum and cerebrospinal fluid samples from five patients with neuro-Behçet's syndrome. Another five patients with non-inflammatory neurological diseases were also studied as a control group. Anticardiolipin antibodies, especially the IgM isotype, and IL-6 were highly elevated in the cerebrospinal fluid of patients with neuro-Behçet's. Levels of both IgM isotype anticardiolipin antibodies and IL-6 in the cerebrospinal fluid dropped after disease activity subsided. These results suggest that the increase in IgM isotype anticardiolipin antibodies and IL-6 in cerebrospinal fluid may be involved in the immune response of neuro-Behçet's within the central nervous system. Serial measurements of IgM isotype anticardiolipin antibodies and IL-6 in the cerebrospinal fluid may be useful in evaluating disease activity in neuro-Behçet's.

Antiganglioside antibodies in patients with neuropsychiatric systemic lupus erythematosus.

Antiganglioside antibodies (AGA) were determined in sera and cerebrospinal fluids (CSF) from 50 systemic lupus erythematosus (SLE) patients, and age-matched normal controls. The SLE patients were subdivided according to the type of clinical manifestation into two groups: neuropsychiatric SLE and active SLE without neuropsychiatric manifestation. The presence of these antibodies showed a significant correlation between IgG AGA in the CSF and IgM AGA in the serum and neuropsychiatric SLE. Fifteen patients had this antibody in the CSF without detectable levels in the serum. No correlation was seen between anticardiolipin antibodies in the serum of CSF and neuropsychiatric SLE. The present work suggests that antibodies against gangliosides may be a marker for neuropsychiatric SLE and that intrathecal antibody production can result in the development of this manifestation.