Serum and Cerebrospinal Fluid Testing in Optic Neuropathy Patients with Malignant Tumors.

PURPOSE: To evaluate the value of serum and cerebrospinal fluid (CSF) testing in optic neuropathy (ON) patients with malignant tumors. METHODS: Fourteen patients clinically diagnosed as ON with malignant tumors but without intracranial or orbital mass in MRI were included in this study. Detailed medical records including medical history, complete ophthalmic examination, colour fundus photography, visual field test, orbital MRI examination, serum and CSF testing data were collected and analyzed. The diagnosis of paraneoplastic optic neuropathy (PON) based on the 2004 recommended criteria of the paraneoplastic syndrome- Euronetwork consortium for paraneoplastic neurological disorders, and current adaption for neuropathies. All patients underwent serum tests for pathogens and autoantibodies including antinuclear antibodies, anticardiolipin antibodies, antineutrophil cytoplasmic antibodies, AQP4-Ab and MOG-Ab, as well as CSF tests for malignant cells under microscope. Serum paraneoplastic antibodies were detected in PON patients. Monkey cerebellar tissue-based assay was used to detect unknown serum anti-neuron antibodies in PON patients with negative paraneoplastic antibody testing results. RESULTS: Fourteen ON patients were classified as four groups based on their clinical and MRI characteristics, as well as serum and CSF testing results: [1] definite PON, 6 cases (11 eyes); [2] possible PON, 3 case (5 eyes); [3] meningeal carcinomatosis-associated optic neuropathy (MCON), 4 cases (6 eyes); [4] infiltrative optic neuropathy (ION), 2 cases (2 eyes). Malignant cells were found under microscope in CSF samples from MCON and ION patients, contrast to no malignant cells in CSF samples from PON cases. All 14 ON patients with malignant tumors showed negative results in serum tests for pathogens and autoantibodies. Serum paraneoplastic antibodies were tested in PON patients, anti- CV2, anti-Yo, and anti- amphiphysin were detected positive in 2, 1, and 1 case, respectively, in definite PON group, whereas no serum paraneoplastic antibody detected in possible PON group. Two unknown serum antineuronal antibodies (an anti- Purkinje cell antibody and an anti-granular cell antibody) were detected using monkey cerebellar tissue-based assay in 2 of 5 PON patients with negative paraneoplastic antibody test results. CONCLUSIONS: Serum and CSF tests are of great importance in differentiating different subtypes of ON with malignant tumors. Current diagnosis of PON still depends on combination of clinical and MRI manifestations, as well as serum and CSF tests. Tissue-based assay may help to detect new biomarkers for ON etiology and diagnosis.

Clinical manifestations and cerebrospinal fluid status in ocular syphilis in HIV-Negative patients.

BACKGROUND: Syphilis with ocular involvement has reemerged as a critical health problem. The aim of the present study was to explore the clinical manifestations and cerebrospinal fluid (CSF) status in ocular syphilis in human immunodeficiency virus (HIV)-negative patients. METHODS: The clinical records of patients with ocular syphilis presenting to the Shanghai Xuhui Central Hospital in the period from January 2011 to December 2012 were retrospectively reviewed. RESULTS: The median age of 25 HIV-negative patients with ocular syphilis was 53 years, 18 patients (72.0 %) were males and 7 (28.0 %) were females. None of them self-identified themselves as men who had sex with men (MSM). The ocular lesions included: uveitis (13 cases), optic neuropathy (6 cases), retinal vasculitis (5 cases), retinal detachment (3 cases), and neuroretinitis (4 cases). Serum toluidine red unheated serum test (TRUST) titer ranged from 1 to 512, with a median of 64. Overall, 18 (72.0 %) of the 25 patients had abnormal CSF results, 15 (60.0 %) CSF samples had elevated white blood cell counts, 13 (52.0 %) had elevated protein levels, and 9 (36.0 %) had reactive CSF Venereal Disease Research Laboratory (VDRL) test, respectively. Mann-Whitney U tests showed higher serum TRUST titer (>32) correlated with the abnormal CSF results. CONCLUSIONS: The demographic characteristics of patients with ocular syphilis in this study were different from previous reports. The study showed a high CSF abnormal rate in HIV-negative patients. The recommendation for CSF examination from all patients with ocular syphilis, including HIV-negative cases, is strongly supported by the present data.

L-PGDS (betatrace protein) inhibits astrocyte proliferation and mitochondrial ATP production in vitro.

L-PGDS is the most abundant protein present in the cerebrospinal fluid (CSF). Although CSF was believed to be homogenous in content, a previous study has showed that a marked concentration gradient of L-PGDS exists between the spinal CSF and the CSF in the subarachnoid space of patients with optic nerve disease (papilledema and normal-tension glaucoma). Astrocytes play a critical role in maintaining the integrity of axon function in the central nervous system and specifically in the optic nerve, and we therefore investigated the biochemical effects of L-PGDS on the proliferation of astrocytes and on the production of adenosine triphosphate (ATP) by astrocyte mitochondria. We found an inhibitory effect of L-PGDS on both proliferation of astrocytes and production of astrocyte ATP. The concentrations that inhibited astrocyte proliferation and ATP production were in the range measured in patients with idiopathic intracranial hypertension and in patients with normal-tension glaucoma. As the CSF is in contact with axons and mitochondria of the optic nerve (Bristow et al. Archives of Ophthalmology, 120, 791-796, 2002), we postulate that a change in the concentration of CSF protein such as L-PGDS could exercise a harmful effect on these structures.

Bilateral optic neuropathy revealing Sjögren's syndrome.

INTRODUCTION: The central nervous system involvement has been reported in 20% of cases of primary Sjogrën's syndrome (SS), a chronic autoimmune disease characterized by a disorder of the exocrine glands secondary to progressive lymphocyte infiltration. Classically described neurological manifestations include sensorimotor deficits, aseptic meningitis or meningoencephalitis, multiple sclerosis-like syndromes and myeolopathies. OBSERVATION: We report here the case of a 53-year-old woman who exhibited rapidly progressive visual loss, disclosing bilateral optic neuropathy, as an uncommon initial symptom of primary SS. Examination of CSF revealed associated aseptic meningitis. Because of the lack of efficacy of the first treatment by intravenous corticosteroids, monthly intravenous cyclophosphamide was quickly introduced. After six months, significant visual recovery was observed. CONCLUSION: Optic neuropathies have been rarely reported as the initial symptom revealing primary Sjogrën syndrome, and bilateral simultaneous lesions remain exceptional.

Brain barrier dysfunction in Cuban epidemic optic neuropathy.

BACKGROUND AND PURPOSE: There are practically no references to cerebrospinal fluid (CSF) studies in tropical or nutritional neuropathies. In the present paper we present the results of CSF studies in patients with Cuban Epidemic Optic Neuropathy (CEON) during epidemic and endemic periods, with an appraisal as to the contribution of brain barriers' function in the pathophysiology of this disease. METHODS: Two hundred and five patients with CEON were studied during the epidemic period (1992-1993) and 12 patients outside the outbreak (1995-1997). CSF protein determination and electrophoresis were carried out, as well as serum and CSF albumin and immunoglobulin G (IgG) quantitation for calculating IgG and Q(alb) indexes, in order to evaluate intrathecal IgG synthesis and the permeability of the blood-CSF barrier (B-CSF B). RESULTS: One fourth of the patients had increased permeability of the B-CSF B, but damage was more frequent between 16 and 60 days from onset of disease, disappearing after 120 days. B-CSF B dysfunction was more prevalent in patients with severe neurological impairment, although it was not related to the severity of ophthalmological damage. The group of patients studied outside of the outbreak (endemic period) showed similar results. DISCUSSION: The possible association of increased permeability of the B-CSF B with oxidative stress, which lies on the basis of this epidemic outbreak, is discussed.

The optic nerve: a new window into cerebrospinal fluid composition?

Cerebrospinal fluid (CSF) pressure and composition are generally thought to be homogeneous within small limits throughout all CSF compartments. CSF sampled during lumbar puncture therefore should be representative for all CSF compartments. On the basis of clinical findings, histology and biochemical markers, we present for the first time strong evidence that the subarachnoid spaces (SAS) of the optic nerve (ON) can become separated from other CSF compartments in certain ON disorders, thus leading to an ON sheath compartment syndrome. This may result in an abnormal concentration gradient of CSF molecular markers determined in locally sampled CSF compared with CSF taken during lumbar puncture.

Amino acid levels and ratios in serum and cerebrospinal fluid of patients with optic neuropathy in Cuba.

Twenty-one amino acids were determined in serum and cerebrospinal fluid of 12 patients with endemic, and in the cerebrospinal fluid of 22 patients with epidemic optic neuropathy. For the endemic patients, there was a decrease in aspartate and taurine in the serum with respect to controls. The ratios aspartate/taurine and taurine/valine were decreased, and glutamate/taurine was increased in the serum. Some of the altered amino acid ratios indicate preponderance of excitatory to inhibitory molecules. The ratio with valine corresponded to the decrease in taurine and the maintenance of valine concentration, an amino acid related to anthropometric parameters. A typical malnutrition pattern was not observed, as the levels of essential amino acids were not significantly modified. In the cerebrospinal fluid there were increases in aspartate, glutamate and threonine, the first two probably indicating a neurodegenerative disorder or some type of metabolic alteration, primary or secondary to the disease. The increase in threonine could be related to lipid metabolism, but it is not clear at present. A wide variety of amino acid ratios were increased in the cerebrospinal fluid of patients with endemic optic neuropathy, mainly pointing to an excitatory condition and some metabolic alterations. In the cerebrospinal fluid of patients with epidemic optic neuropathy there was an increase in aspartate and glutamate, and increase in glutamate/taurine, glutamate/glycine, and gamma-aminobutyric acid/glycine ratios. Interesting differences were also observed between patients from different periods of time, but with the same clinical features, and the modifications of amino acid concentrations in the cerebrospinal fluid, such as glutamine, threonine and tryptophan. The present results indicate a disorder in the metabolism of amino acids, support a specific deficit, especially for taurine, an imbalance between excitatory and inhibitory amino acids, and a possible relation to viral infections.

[Folic acid deficiency and increased concentrations of formate in serum and cerebrospinal fluid of patients with epidemic optical neuropathy]. / Deficiencia de folato y concentraciones elevadas de formato en suero y líquido cefalorraquídeo de pacientes con neuropatía óptica epidémica.

We studied 62 patients aged 48 years as an average and diagnosed with bilateral optical neuropathy during an epidemics in Pinar del Río province. Of these patients, 42 showed the optical form whereas 20 had the mixed form of optical neuropathy. We researched into the levels of formate and folate in serum and cerebrospinal fluid samples and we found a marked deficiency of folates in more than 50% of samples and high formate concentration levels in almost 25% of samples. We concluded that nutritional shortages that lead to a reduction of folates, and the intake of small amounts of methanol in alcoholic drinks could lead to lacking energetic states which would facilitate that the optical nerve be affected and the epidemic optical neuropathy appear.

Macrophage migration inhibitory factor in the cerebrospinal fluid of patients with conventional and optic-spinal forms of multiple sclerosis and neuro-Behçet's disease.

Macrophage migration inhibitory factor (MIF) is becoming increasingly recognized as an important regulator of immune and inflammatory responses. It is released by activated T lymphocytes and macrophages and up-regulates the proinflammatory activity of these cells. MIF is required for antigen- and mitogen-driven T cell activation, and stimulates macrophages to release cytokines and nitric oxide. On the basis of the recent suggestion that pharmacological modulation of MIF production and neutralization of its activity may have important implications for treatment of a variety of autoimmune or inflammatory conditions, we determined the level of MIF in the cerebrospinal fluid (CSF) of patients with conventional-form multiple sclerosis (C-MS) and optic-spinal form multiple sclerosis (OpS-MS), and neuro-Behçet's disease (NBD). As control, the CSF of patients with non-inflammatory neurological diseases (NIND) was used. The concentration of MIF in CSF samples was significantly elevated in relapsed cases of C-MS (4.13+/-1.07 ng/ml) (mean+/-S.D.) compared with control samples (2.38+/-0.60 ng/ml) (P<0.0001), whereas MIF in the CSF of C-MS patients in remission was not elevated (2.65+/-0.67 ng/ml). The concentration of MIF in the CSF of OpS-MS patients in relapse (5.53+/-1.74 ng/ml) was higher than that of patients with C-MS in relapse (P<0.05). In NBD patients, the concentration of MIF in CSF was significantly elevated (7.47+/-5.61 ng/ml) compared with control samples (P<0.01) and correlated well with cell count in these samples (r=0.910, P<0.005). These results suggest that MIF may play a pivotal role in immune-mediated diseases of the central nervous system, and that MIF may be useful in the study of differences between C-MS and OpS-MS.

Deficiencia de folato y concentraciones elevadas de formato en suero y líquido cefalorraquídeo de pacientes con neuropatía óptica epidémica / Folic acid deficiency and increased concentrations of formate in serum and cerebrospinal fluid of patients with epidemic optical neuropathy

We studied 62 patients aged 48 years as an average and diagnosed with bilateral optical neuropathy during an epidemics in Pinar del RÝo province. Of these patients, 42 showed the optical form whereas 20 had the mixed form of optical neuropathy. We researched into the levels of formate and folate in serum and cerebrospinal fluid samples and we found a marked deficiency of folates in more than 50 of samples and high formate concentration levels in almost 25 of samples. We concluded that nutritional shortages that lead to a reduction of folates, and the intake of small amounts of methanol in alcoholic drinks could lead to lacking energetic states which would facilitate that the optical nerve be affected and the epidemic optical neuropathy appear.

Characterization of a virus isolated from the cerebrospinal fluid of patients with epidemic neuropathy.

A previously unknown disease, termed epidemic neuropathy (EN), occurred in Cuba between 1991 and 1993. When samples of cerebrospinal fluid (CSF) from 45 patients with EN and 11 controls were inoculated into cultures of VERO cells, almost all (93%) of the samples from the cases of EN but only one (9%) of the control samples produced a slowly progressing cytopathological effect (CPE). Although the results of other studies indicated the presence of a picornavirus-like virus in CSF samples from EN cases, the CPE and other physico-chemical characteristics observed were not those expected of picorn-viruses. Several aetiological factors may have contributed to EN but at least one virus could have played a major role.

Surgically verified case of optic sheath nerve meningocele: case report with review of the literature.

Optic sheath meningocele is rare; only approximately 31 cases have been reported. The term optic sheath meningocele has recently been proposed by Garrity and Forbes to describe primary CSF cysts of the optic nerve sheath, without apical mass or malformation of the cranio-orbital junction. Presenting symptoms are often related to involvement of the optic nerve, with a slow or rapid decrease of visual acuity. CT and MRI studies reveal a tubular-cystic enlargement of the optic nerve/optic sheath complex (on/onsc), with thickening of the optic nerve. Radiological differential diagnosis should include optic nerve tumors such as gliomas, meningiomas, and arachnoid cysts involving the optic nerve sheath. Up to now, it seems that early surgical management by means of optic nerve/optic nerve sheath decompression affords an improvement of visual function with minimal morbidity in patients who present a rapid decrease of visual acuity within 3-6 months. We present an additional case and discuss the clinical, radiological, and operative features of this pathological condition of the optic nerve sheath.

[Mechanism of Enterovirus participation in epidemic neuropathy. Physiopathological hypothesis]. / Mecanismo de participación de los Enterovirus en la neuropatía epidémica. Hipótesis fisiopatológicas.

During the epidemic neuropathy occurred in Cuba from 1992 to 1993, viral isolations antigenically connected with Coxsackie viruses were obtained from the cerebrospinal fluid of patients. Virological, epidemiological, toxicologic, nutritional, immunological and histopathological investigations were made. Though the disease was related to toxic and nutritional factors, it has been impossible to identify the cause of the epidemic. Taking into consideration the results of the different investigations, we have formulated a comprehensive and multifactorial hypothesis to explain the physiopathological mechanism of the participation of the isolated viruses as mediators in a process of autoimmunity of the pathogeny of the disease.

Optic nerve sheath meningoceles. Clinical and radiographic features in 13 cases with a review of the literature.

Thirteen patients with dilated intraorbital optic nerve sheaths with an expanded, patulous cerebrospinal fluid (CSF) space were studied with high-resolution computed tomography (CT) or magnetic resonance imaging (MRI). Eleven patients had bilateral findings. Headache or visual complaints, or both, were present in all patients. Signs of optic nerve dysfunction were present in eight patients. Three patients had visual acuity worse than 20/200. Cerebrospinal fluid pressure was mildly elevated in two patients. Three patients underwent a surgical procedure; visual acuity improved in one. The authors propose the term meningocele for this condition and suggest MRI with fat-suppression techniques and off-axis sagittal views as the radiographic procedure of choice.