Intrathecal gadolinium-enhanced magnetic resonance myelography in the detection of CSF leak.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
Cris S Constantinescu
Publications and source records attributed to Cris S Constantinescu.
Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.
Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.
Brain↗
Effects of glucocorticoids on STAT4 activation in human T cells are stimulus-dependent.
Glucocorticoids affect the immune system by a number of mechanisms, including modulation of cytokine production in lymphocytes. Glucocorticoids suppress T helper cell type 1 immune responses by decreasing the ability of T cells to respond to interleukin (IL)-12, a major inducer of interferon (IFN)-gamma. IFN-beta increases the expression of the anti-inflammatory cytokine IL-10 and suppresses IL-12. Signaling pathways through IFN-beta and the IL-12 receptor (IL-12R) involve activation by phosphorylation of signal transducer and activator of transcription 4 (STAT4). Our aim was to investigate the effects of dexamethasone on STAT4 activation by IFN-beta and IL-12 in human T cell blasts. We report that dexamethasone decreases IL-12-induced STAT4 phosphorylation and IFN-gamma production and enhances IFN-beta-induced STAT4 activation and IL-10 production. These effects are associated with a down-regulation of IL-12Rbeta1 expression but an up-regulation of IFN-betaR. These results indicate that the effect of glucocorticoids on the STAT4 signaling pathway depends on the stimulus activating that pathway.
Dexamethasone↗
'Importance sampling' in MS: use of diffusion tensor tractography to quantify pathology related to specific impairment.
Specific neurological impairments in multiple sclerosis (MS) are dependent on the pathology in clinically eloquent areas of the central nervous system. We aimed to use diffusion tensor fiber tracking to identify the pyramidal tracts and corpus callosum in MS patients, measure the apparent diffusivity within the tracts, and evaluate whether this would correlate with relevant disability scores. Dual-echo and diffusion tensor magnetic resonance imaging (DT-MRI) brain scans were obtained from 29 patients with relapsing remitting MS, and 13 age and gender matched normal controls. Voxels from pyramidal tracts and corpus callosum were automatically identified using a tractography based algorithm. Mean apparent diffusion coefficient (ADC(av)) was measured for these tracts. Scores of Expanded Disability Status Scale (EDSS) and Paced Auditory Serial Addition Test (PASAT) were obtained. The median EDSS score was 2.5 (inter-quartile range 2-3.25). The ADC(av) in the pyramidal tracts (p=0.02) and corpus callosum (p=0.0004) in patients was significantly higher than in controls. Pyramidal tracts ADC(av) was correlated with pyramidal FSS (r=0.5, p=0.008). Corpus callosum ADC(av) was correlated with PASAT (r=-0.58, p=0.001). Global T2 lesion volume did not correlate with the EDSS, but correlated with ADC(av) of the pyramidal tracts (r=0.6, p=0.0007) and corpus callosum (r=0.8, p<0.0001). T2 lesion volume within the pyramidal tracts and corpus callosum correlated with ADC(av) in the pyramidal tracts (r=0.6, p=0.0009) and corpus callosum (r=0.65, p=0.0002) respectively, but not with pyramidal FSS or PASAT score. DT-MRI quantifies pathology in specific white matter tracts and may increase the specificity of MRI in monitoring progression of motor and cognitive deficits in MS.
Acoustic Stimulation↗
Astrocytes as antigen-presenting cells: expression of IL-12/IL-23.
Interleukin-12 (IL-12, p70) a heterodimeric cytokine of p40 and p35 subunits, important for Th1-type immune responses, has been attributed a prominent role in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Recently, the related heterodimeric cytokine, IL-23, composed of the same p40 subunit as IL-12 and a unique p19 subunit, was shown to be involved in Th1 responses and EAE. We investigated whether astrocytes and microglia, CNS cells with antigen-presenting cell (APC) function can present antigen to myelin basic protein (MBP)-reactive T cells, and whether this presentation is blocked with antibodies against IL-12/IL-23p40. Interferon (IFN)-gamma-treated APC induced proliferation of MBP-reactive T cells. Anti-IL-12/IL-23p40 antibodies blocked this proliferation. These results support and extend our previous observation that astrocytes and microglia produce IL-12/IL-23p40. Moreover, we show that stimulated astrocytes and microglia produce biologically active IL-12p70. Because IL-12 and IL-23 share p40, we wanted to determine whether astrocytes also express IL-12p35 and IL-23p19, as microglia were already shown to express them. Astrocytes expressed IL-12p35 mRNA constitutively, and IL-23 p19 after stimulation. Thus, astrocytes, under inflammatory conditions, express all subunits of IL-12/IL-23. Their ability to present antigen to encephalitogenic T cells can be blocked by neutralizing anti-IL-12/IL-23p40 antibodies.
Animals↗
Measurement of cervical spinal cord cross-sectional area by MRI using edge detection and partial volume correction.
PURPOSE: To detail a procedure to accurately measure upper cervical cord cross-sectional area (CSA), using MRI, by correcting for partial volume averaging (PVA), and to assess the usefulness of the procedure for measuring cervical cord atrophy rates in longitudinal studies. MATERIALS AND METHODS: Analysis of errors associated with measuring CSA in the presence of PVA is given. A numerical phantom image is produced, including simulated acquisition noise, to assess accuracy of the method in idealized conditions, and to verify the results of the error analysis. A phantom, consisting of 11 rods of known CSA, was scanned 10 times and measurement accuracy assessed. A total of 10 normal subjects were scanned twice to assess the reproducibility under experimental conditions. RESULTS: The measurement error for the numerical phantom increased with increased simulated acquisition noise, as predicted by the analysis. Measurement of the plastic phantom revealed a systematic overestimate in CSA due to limited scanner accuracy of 3.15%. The scan-rescan error for the CSA of the cervical spine in the 10 normal subjects was 0.55%. CONCLUSION: Correcting for PVA allows accurate measurement of the upper cervical cord CSA and accurate measurement of a standard phantom to guard against scanner drift in longitudinal studies of cord CSA.
Algorithms↗
Spinal cord imaging in multiple sclerosis.
Multiple sclerosis (MS) is a chronic neurological condition characterized pathologically by axonal loss, demyelination, inflammation, and gliosis. Magnetic resonance imaging (MRI) has had a major impact on diagnosing MS, understanding the condition, and monitoring the effects of treatments. Recently, spinal cord MRI has received increased attention. Advanced techniques have been used to image the spinal cord, particularly the cervical cord, and measure quantitative parameters such as T1 relaxation time, magnetization transfer ratio, and diffusivity. These metrics show central nervous system abnormalities in MS patients and various correlations with disability and might reflect specific pathological processes. Image analysis techniques have also been developed and combined with high-resolution MRI to measure the cord cross-sectional area (CSA), a metric that relates to cord atrophy. The cord CSA is reduced in MS patients compared to normal controls and correlates with disability. Furthermore, changes in CSA are detectable and correlate with changes in disability. Despite the technical difficulties of performing spinal cord MRI, imaging studies, particularly of the cervical cord, are becoming more common. Significant focus has been placed on measuring cord atrophy, and reproducible techniques have been developed to measure the cervical cord CSA. Spinal cord MRI may provide information about disease progression that is not readily available from brain MRI scans and could be useful in diagnosing MS in some cases, as well as for monitoring the effects of treatments.
Atrophy↗
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.
Adult↗
Measurement of spinal cord atrophy in multiple sclerosis.
In multiple sclerosis (MS), the spinal cord is a common area of involvement, and its dysfunction is likely to be responsible for much of motor disability. It has been reported that atrophy in the cervical spinal cord occurs early and is detectable in patients presenting with a clinically isolated syndrome. This finding has important implications for the early treatment of patients with MS because atrophy is thought to reflect destructive, irreversible pathology and subclinical impairment. Recent clinical trials of disease-modifying agents have included spinal cord imaging and, in particular, the measurement of atrophy as a secondary or exploratory measure of treatment efficacy. This review summarizes the underlying pathology responsible for spinal cord atrophy and the methods available to measure it. The relationships between spinal cord atrophy, other magnetic resonance imaging parameters, and clinical disability are also discussed.
Atrophy↗
Magnetic resonance imaging of the cervical spinal cord in multiple sclerosis--a quantitative T1 relaxation time mapping approach.
BACKGROUND: The spinal cord is a common site of involvement in multiple sclerosis (MS) where pathology contributes substantially to locomotor disability. Previous studies have demonstrated significant correlations between clinical disability and cervical cord atrophy, but not with cord T(2) lesion load. We evaluate cervical cord pathology using, for the first time, quantitative T(1) relaxation time (T(1)), which shows histopathological specificity for tissue damage in the cerebral white matter. METHOD: Cervical cord T(1) was compared in 15 MS patients [8 relapsing-remitting (RR), 7 secondary progressive (SP)] and 6 healthy controls, and related to normalised upper cervical cord area (UCCa), cerebral white matter T(1), T(2) lesion load and disability measures including the Expanded Disability Status Scale (EDSS), Ambulation index (AI) and timed 25-foot walk. T1 maps of the brain and cervical cord were acquired using a high-resolution, 3-dimensional fast low-angle shot sequence. Dual-echo sequences were also obtained. RESULTS: Median cervical cord T(1) [mean (standard deviation)] was significantly greater in RR [854 [28] ms] (p = 0.0006) and SP patients [927 [67] ms] (p < 0.0001) compared with controls [888 [61] ms], and in SP vs. RR patients (p = 0.002). In the overall patient cohort, it correlated significantly with median cerebral white matter T1 (r = 0.7, p = 0.0046), UCCa (r = -0.87, p < 0.0001), but not T2 lesion loads. Both median cervical cord T1 and UCCa (respectively) correlated significantly with the EDSS (r = 0.55, p = 0.03; r = -0.54, p = 0.04), AI (r = 0.77, p = 0.001; r = -0.60, p = 0.02) and timed 25-foot walk (r = 0.56, p = 0.03; r = -0.55, p = 0.04). CONCLUSION: Cervical cord T(1) distinguishes between MS subgroups and could also prove a useful surrogate outcome measure in MS. The relation of cervical cord T(1) to cerebral white matter T(1) suggests that cord pathology may be influenced by tissue damage upstream.
Adult↗
Skeletal muscle myosin is the autoantigen for experimental autoimmune myositis.
Experimental autoimmune myositis (EAM) is a rodent model for human inflammatory muscle disease (IMD). It can be induced by immunization of rodents with skeletal muscle homogenate and adjuvant. The specific myositogenic autoantigen has not been clearly identified although some evidence points to skeletal muscle myosin. In this report we strengthen this evidence, showing that Lewis rats immunized with purified skeletal muscle myosin develop EAM with the same pattern and severity as EAM induced by whole rabbit skeletal muscle homogenate (WRM). Multiple inflammatory lesions are detected histopathologically in the biceps, quadriceps, and gastrocnemius muscles. Myosin-reactive T cells from animals immunized either with myosin or with WRM have similar patterns of antigen-induced proliferation. The results show that myosin, a component of skeletal muscle, is at least one autoantigen in EAM.
Animals↗
Combined pharmacologic and surgical approach to acquired nystagmus due to multiple sclerosis.
PURPOSE: To describe a combined pharmacological and surgical approach to treating acquired nystagmus in a patient with multiple sclerosis. DESIGN: Interventional case report. METHODS: A 40-year-old patient with acquired horizontal and vertical nystagmus and severe oscillopsia secondary to multiple sclerosis had combined treatment with gabapentin and a vertical Kestenbaum-type procedure. RESULTS: After gabapentin treatment (3,000 mg orally daily) the horizontal nystagmus was significantly reduced, and the patient developed a marked chin-up position. The vertical nystagmus remained unchanged, dampening on downgaze. A recession of both inferior rectus muscles reduced the nystagmus significantly in primary position, the abnormal head position disappeared, and oscillopsia completely resolved. Treatment increased visual acuity from 6/24 in the right eye and 6/60 in the left eye to 6/9 in both eyes. CONCLUSIONS: Acquired nystagmus in multiple sclerosis can be significantly improved by using a combined pharmacological and surgical approach.
Acetates↗
Migraine and Raynaud phenomenon: possible late complications of Kawasaki disease.
Migraine and Raynaud phenomenon often coexist and may reflect similar vascular reactions. Both have been associated with vascular endothelial cell dysfunction. Kawasaki disease is a systemic vasculitis of unknown etiology that affects children and may lead to the formation of coronary artery aneurysms. Endothelial cell dysfunction has been demonstrated late in Kawasaki disease and is not restricted to coronary vessels. We report the case of a patient who developed typical migraine with aura and Raynaud phenomenon at the age of 14, 12 years after onset of Kawasaki disease. His migraine responded well to pizotifen, and both migraine and Raynaud phenomenon improved after initiation of treatment with valproic acid. We postulate that both migraine and Raynaud phenomenon in this case represent late consequences of Kawasaki disease and result from extracoronary endothelial dysfunction.
Adult↗
Oscillopsia without nystagmus caused by head titubation in a patient with multiple sclerosis.
Oscillopsia in patients who have brain stem disorders but not nystagmus is attributed to a failure of the vestibular-ocular reflex (VOR) to compensate for head movements. We report a patient who had marked head titubation and oscillopsia in aggressive multiple sclerosis but no nystagmus. Her severe head titubation precluded our ability to measure a VOR accurately. Because oscillopsia has also been described after rapid voluntary head oscillations in normal subjects, we queried whether the oscillopsia in our patient could be ascribed to the head movement alone. Six normal control subjects did not experience oscillopsia while shaking their heads at the same frequency as the patient's titubation. We conclude that the oscillopsia in our patient was probably the result of an impaired VOR or an alternative compensatory mechanism.
Adult↗