mtDNA haplogroup J: a contributing factor of optic neuritis.
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Optic neuritis frequently occurs in multiple sclerosis (MS), and shares several similarities with the optic neuritis of Leber's hereditary optic neuropathy (LHON), which is mainly due to maternally transmitted mitochondrial DNA (mtDNA) mutations. Our report shows for the first time that a mitochondrial DNA background could influence the clinical expression of MS. One European mtDNA haplogroup was found only in MS patients with optic neuritis but not in MS patients without visual symptoms. Therefore, we hypothesize that mtDNA haplogroup J might constitute a risk factor for optic neuritis occurrence when it is coincidentally associated with MS, but not be a risk factor for developing MS per se as suggested previously. (+info)
Correlation between morphological and functional retinal impairment in multiple sclerosis patients.
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PURPOSE: To assess whether a correlation exists between optic nerve fiber layer (NFL) thickness and the retinal or visual pathway function in multiple sclerosis (MS) patients previously affected by optic neuritis. METHODS: Fourteen patients with a diagnosis of definite MS were examined. All had been affected by optic neuritis (MSON) with complete recovery of visual acuity (14 eyes included in study). These were compared with 14 eyes from 14 age-matched control subjects. NFL thickness was measured by optical coherence tomography (OCT). Three different measurements in each quadrant (superior, inferior, nasal, and temporal) were taken and averaged. The data in all quadrants (12 values averaged) were identified as NFL Overall, whereas the data obtained in the temporal quadrant only (3 values averaged) were identified as NFL Temporal. Retinal and visual pathway function was assessed by simultaneously recording pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) using high-contrast (80%) checkerboard stimuli subtending 15 minutes and 60 minutes of the visual arc (min arc) and reversed at the rate of two reversals per second. RESULTS: In MSON eyes there was a significant (P < 0.01) reduction in NFL thickness in both NFL Overall and NFL Temporal evaluations compared with the values observed in control eyes. PERG, (15-min arc checks) and VEP (15-min arc and 60-min arc checks), showed a significant (P < 0.01) delay in latency and reduction in amplitude. NFL Overall and NFL Temporal values were significantly correlated (P < 0.01) to the PERG P50 latency and P50 to N95 amplitude recorded with 15-min arc checks. No correlations (P > 0.01) between NFL values and the other electrophysiological data (PERG recorded with 60-min arc checks and VEP recorded with 15-min arc and 60-min arc checks) were found. CONCLUSIONS: There is a correlation between PERG changes and NFL thickness in MS patients previously affected by optic neuritis, but there is no correlation between VEP changes and NFL thickness. (+info)
Lack of restriction of T cell receptor beta variable gene usage in cerebrospinal fluid lymphocytes in acute optic neuritis.
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OBJECTIVES: There have been many studies reporting restricted patterns of T cell receptor usage in established multiple sclerosis and these have led to clinical trials of immunomodulation directed at deleting clonal T cell populations. The present study aims to test the hypothesis that highly restricted T cell populations are also present in the CSF in the earliest clinical stages of acute demyelinating disease of the CNS. METHODS: T cell receptor Vbeta (TCRBV) gene expression was studied in CSF and blood in nine patients with acute optic neuritis within 7 days of onset of symptoms, six patients with an acute relapse of multiple sclerosis, and 13 control subjects. RNA was extracted and cDNA synthesised from unstimulated CSF and blood lymphocytes, and TCRBV gene segments were amplified from the cDNA by polymerase chain reaction (PCR) using 21 family specific primers. PCR products were separated by polyacrylamide gel electrophoresis and detected via a labelled oligonucleotide probe. A semiquantitative analysis of band intensity was performed by laser densitometry. RESULTS: TCRBV mRNA was detected in the CSF of eight of nine patients with optic neuritis, six of six patients with multiple sclerosis, and five of 13 controls, and was closely correlated with the presence of oligoclonal IgG. Usage of a single TCRBV family was demonstrated in two of nine patients with optic neuritis and two of six patients with multiple sclerosis. The number of TCRBV families expressed in the other patients ranged between 5 and 15 (optic neuritis) and 4 and 17 (multiple sclerosis). CONCLUSIONS: There is a relative lack of restriction of TCRBV usage by CSF lymphocytes in the very earliest stages (<7 days) of acute optic neuritis. This may imply either that multiple sclerosis is not a monoclonal disease even at onset, or that the autoimmune response has widened before the disease becomes clinically evident. This may have important consequences for the design of immune therapies in multiple sclerosis. Further studies are required to determine whether the CSF T cell repertoire at presentation has prognostic importance. Longitudinal studies are required to follow the CSF T cell repertoire from the time of presentation and to determine whether it may have prognostic significance. (+info)
Demonstration of Bartonella grahamii DNA in ocular fluids of a patient with neuroretinitis.
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We describe the clinical and laboratory features of a 55-year-old human immunodeficiency virus-negative female patient who presented with bilateral intraocular inflammatory disease (neuroretinitis type) and behavioral changes caused by a Bartonella grahamii infection. Diagnosis was based on the PCR analysis of DNA extracted from the intraocular fluids. DNA analysis of the PCR product revealed a 100% identity with the 16S rRNA gene sequence of B. grahamii. The patient was successfully treated with doxycycline (200 mg/day) and rifampin (600 mg/day) for 4 weeks. This is the first report that demonstrates the presence of a Bartonella species in the intraocular fluids of a nonimmunocompromised patient and that indicates that B. grahamii is pathogenic for humans. (+info)
Combined fat- and water-suppressed MR imaging of orbital tumors.
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BACKGROUND AND PURPOSE: The use of a high-resolution T2-weighted MR sequence, which suppresses signal from both fat and water, has been shown to be highly effective for depicting areas of inflammatory damage within the optic nerve. The ability of this sequence to show neoplastic and inflammatory orbital lesions, which may mimic neuritis, is unknown. This study was designed to examine the characteristics of such a sequence for the investigation of orbital mass lesions. METHODS: Twenty-eight patients with known or suspected mass lesions of the orbit and six healthy volunteers were recruited for study. Imaging was performed with a 1.5-T MR unit. Participants were examined by selective partial inversion recovery (SPIR) sequences with T2-weighted fast spin-echo acquisition, selective partial inversion recovery/fluid attenuated inversion recovery (SPIR/FLAIR) sequences with fast spin-echo acquisition, short tau inversion recovery (STIR) sequences with fast spin-echo acquisition, and SPIR sequences with contrast-enhanced T1-weighted fast spin-echo acquisition. Two neuroradiologists, using a randomised, blinded method, scored images for lesion presence and extent. Lesion extent was defined as the number of images with visible abnormality, and was compared with the standard of reference established at a later date by consensus review of all imaging sequences. The ability of the sequences to show the presence and extent of pathologic lesions was compared. RESULTS: The SPIR/FLAIR sequence showed both the presence and extent of orbital masses significantly better than did either STIR or T2-weighted SPIR sequences (P<.01 and P<.001, respectively). Contrast-enhanced T1-weighted SPIR images ranked better than SPIR/FLAIR images, although the difference failed to reach statistical significance. In the orbital apex, the SPIR/FLAIR technique was superior to all other techniques used. This reflected its ability to distinguish enhancing, pathologic lesions from enhancing, normal anatomy. CONCLUSION: SPIR/FLAIR is an appropriate screening technique for orbital masses and offers significant advantages over currently used fat-suppressed sequences for the investigation of orbital disease. (+info)
Multiple sclerosis: the disease and its manifestations.
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Multiple sclerosis is an immune-mediated inflammatory demyelinating disease of the central nervous system clinically characterized by relapses and remissions of neurological disturbance. A typical relapse, exemplified by optic neuritis, increases in severity over a week or two and after approximately one month begins to remit. Resolution takes place over the course of two to three months. In the early stages, clinical recovery is virtually complete, though persistent abnormalities of conduction can usually be detected by evoked potential techniques and persistent structural abnormalities can be detected by magnetic resonance imaging (MRI). These techniques, together with cerebrospinal fluid examination for oligoclonal IgG, provide supporting evidence for the diagnosis which, in the absence of a specific test, nevertheless remains primarily clinical. The course of the disease is very variable, but after a number of years neurological deficit begins to accumulate after each relapse. In most patients, the relapsing and remitting phase of the disease is followed by a phase of continuous progression of disability. Cognitive disturbances can be detected in many patients even quite early in the course of the illness. Deficits in attention, memory and executive skills may be prominent and tend to become increasingly prominent as neurological deficit increases, although this is not always the case. There is some correlation between the extent of MRI abnormalities in the cerebral white matter and the severity of cognitive deficit. Depression and anxiety are commonly experienced but are poorly correlated to the lesion load seen on MRI. In contrast, the much rarer psychotic symptoms, euphoria and emotional lability are closely linked to the severity of white matter disease. (+info)
Response variability in the visual field: comparison of optic neuritis, glaucoma, ocular hypertension, and normal eyes.
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PURPOSE: To compare the relationship between sensitivity and response variability in the visual field of normal eyes and eyes with optic neuritis (ON), glaucoma (POAG), and ocular hypertension (OHT). METHODS: Frequency-of-seeing (FOS) data were collected from four visual field locations in one eye of 71 subjects (12 ON, 25 POAG, 11 OHT, and 23 normal), using a constant stimulus method on an Henson 4000 perimeter (Tinsley Instruments, Croydon, UK). At each location, at least 20 stimuli (subtending 0.5 degrees) were presented for 200 ms at six or more intensities above and below the estimated threshold. The mean and SD of the probit fitted cumulative Normal function were used to estimate sensitivity and response variability. Cluster regression analysis was carried out to determine whether there were differences in the sensitivity-log (variability) relationship between the four groups. RESULTS: Variability was found to increase with decreased sensitivity for all four groups. The combined data from the four groups was well represented (R2 = 0.57) by the function log(e)(SD) = A.sensitivity (dB) + B, where the constants A and B were -0.081 (SE, +/-0.005) and 3.27 (SE, +/-0.15), respectively. Including other statistically significant covariates (false-negative errors, P = 0.004) and factors (diagnosis, P = 0.005) into the model increased the proportion of explained variance to 62% (R2 = 0.62). Stimulus eccentricity (P = 0.34), patient age (P = 0.33), fixation loss rate (P = 0.10), and false-positive rate (P = 0.66) did not reach statistical significance as additional predictors of response variability. CONCLUSIONS: The relationship between response variability and sensitivity is similar for ON, POAG, OHT, and normal eyes. These results provide supporting evidence for the hypothesis that response variability is dependent on functional ganglion cell density. (+info)
Recovery from optic neuritis is associated with a change in the distribution of cerebral response to visual stimulation: a functional magnetic resonance imaging study.
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OBJECTIVES: Recovery to normal or near normal visual acuity is usual after acute demyelinating optic neuritis, despite the frequent persistence of conduction abnormalities as evidenced by the visual evoked potential (VEP). This raises the possibility that cortical adaptation to a persistently abnormal input contributes to the recovery process. The objective of this study was to investigate the pattern of cerebral response to a simple visual stimulus in recovered patients in comparison to normal subjects. METHODS: Functional magnetic resonance imaging (fMRI) was used to study the brain activation pattern induced by a periodic monocular 8Hz photic stimulus in seven patients who had recovered from a single episode of acute unilateral optic neuritis, and in seven normal controls. VEPs and structural optic nerve MRI were performed on patients. RESULTS: Stimulation of either eye in controls activated only the occipital visual cortex. However, in patients, stimulation of the recovered eye also induced extensive activation in other areas including the insula-claustrum, lateral temporal and posterior parietal cortices, and thalamus; stimulation of the clinically unaffected eye activated visual cortex and right insula-claustrum only. The volume of extraoccipital activation in patients was strongly correlated with VEP latency (r = 0.71, p = 0.005). CONCLUSIONS: The extraoccipital areas that were activated in patients all have extensive visual connections, and some have been proposed as sites of multimodal sensory integration. The results indicate a functional reorganisation of the cerebral response to simple visual stimuli after optic neuritis that may represent an adaptive response to a persistently abnormal input. Whether this is a necessary part of the recovery process remains to be determined. (+info)