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Biomedical subjects

C S Constantinescu

Publications and source records attributed to C S Constantinescu.

At least 19 recordsLinked to original sources
PubMed2006

Deep gray matter and fatigue in MS: a T1 relaxation time study.

UNLABELLED: Fatigue in multiple sclerosis (MS) occurs commonly, sometimes as the earliest symptom. Some MS patients consider fatigue to be their most troublesome complaint, and it has been shown to be an independent predictor of impaired quality of life. Several reports have demonstrated that subcortical gray matter pathology is related to fatigue. We hypothesized that MRI detectable changes in the deep gray matter of MS patients may correlate with fatigue severity. Our objective was: to assess the relationship between fatigue severity and detectable changes on magnetic resonance imaging (MRI), quantified using the mean T1 relaxation time (T1), in deep gray matter structures in relapsing remitting multiple sclerosis (RRMS). Using region of interest analysis, T1 values were measured for the thalamus, putamen and caudate nucleus in 52 RRMS patients and 19 healthy volunteers. Fatigue was assessed using the Fatigue Severity Scale. RESULTS: The median T1 in the thalamus and the putamen were significantly higher in the patient cohort than in the healthy controls; the median T1 in the caudate was also higher in the MS patients but did not reach statistical significance. There was a significant correlation between fatigue severity and the T1 of the thalamus (rho = 0.418; p = 0.014). Furthermore, the median T1 in the thalamus was significantly higher in patients with fatigue compared with those without (p = 0.018). Our results provide further evidence for the role of subcortical gray matter structures in the pathogenesis of multiple sclerosis (MS)-related fatigue. This study also demonstrates that T1 relaxation time measurement is a suitable technique for detecting abnormalities of the deep gray matter in RRMS and presents further support of gray matter involvement in MS.

Adult↗
PubMed2006

Atopic optic neuritis.

PURPOSE: To report a case of optic neuritis associated with atopic dermatitis, which may represent an optic nerve counterpart of atopic myelitis. METHODS: Clinical examination, MRI, blood investigations. RESULTS: A 34-year-old man with severe atopic dermatitis developed a steroid-responsive bilateral optic neuritis. Serum IgE was highly elevated, with high titers of mite-specific IgE. Clinical ophthalmological fluctuations paralleled those of atopic dermatitis. CONCLUSIONS: The clinical features and parallel fluctuations strongly suggest that the patient's optic neuritis was related to atopic dermatitis. This atopic optic neuritis may represent the optic nerve equivalent of atopic myelitis.

Adult↗
PubMed2005

Corpus callosum changes following shunting for hydrocephalus: case report and review of the literature.

Diffuse callosal signal changes can rarely occur following successful shunting for obstructive hydrocephalus. We report on a patient who underwent ventriculoperitoneal shunting for aqueductal stenosis and required two revisions for neurological deterioration and presumed shunt malfunction. Extensive changes involving the corpus callosum, periventricular white matter and optic chiasm were noted after the first, and were prominent after second shunt revision. Thus, post-shunting callosal changes may be associated with more extensive white matter disease, and may not imply wide pressure fluctuations. However, they need not prompt further intervention.

Adult↗
PubMed2004

Serum uric acid levels in optic neuritis.

Uric acid, an antioxidant, is reduced in multiple sclerosis (MS). Patients with gout have a reduced incidence of MS. Optic neuritis (ON), often the first manifestation of MS, is not known to be associated with reduced uric acid. Patients with recent onset of ON were investigated to determine whether uric acid levels were reduced at presentation. Twenty-one patients with ON were included, 17 females and 4 males. The mean (SD) serum uric acid in the ON female group was 184.4 ( +/-55.1) micromol/L (range, 116-309 micromol/L), whilst in the control group it was 235.2 (+/- 50.2) micromol/L (range, 172-381 micromol/L). The difference was statistically significant (chi2 = 8.93, P = 0.003). In the small male cohort, mean (SD) serum uric acid was 305 (+/- 52.1) micromol/L, whilst in the control group it was 328 (+/- 80.4) micromol/L. These differences were not statistically significant. Reduced antioxidant reserve is possibly an early pathogenic mechanism in inflammatory demyelination, and raises the possibility that low uric acid levels could be an indicator of disease activity. Since optic neuropathies of other causes were not investigated, future research needs to determine whether low uric acid represents a unique feature of optic neuritis or is seen in other optic neuropathies.

Adult↗
PubMed2004

A prospective study of conditions associated with multiple sclerosis in a cohort of 658 consecutive outpatients attending a multiple sclerosis clinic.

The cause of multiple sclerosis (MS) remains unknown. It is largely regarded as being an inflammatory autoimmune disease and has been reported in association with other inflammatory/autoimmune diseases. We performed a prospective study in 658 consecutive patients diagnosed with MS attending our outpatient MS management clinic between June 2002 and June 2003. Prevalence of associated conditions in these patients was calculated and compared with values from population studies using chi-square tests, odds ratios and confidence intervals. The MS population had significantly increased rates of asthma, inflammatory bowel disease, type 1 diabetes mellitus, pernicious anaemia, autoimmune thyroid disease, uveitis, seronegative spondyloarthropathies, bipolar disorder and melanoma compared to the general population. Both T helper type 1 (Th1)-mediated and T helper type 2 (Th2)-mediated diseases were significantly increased compared to the general population. There were also interesting associations seen with polyglandular autoimmune syndrome and rare single case associations. MS is associated with several other conditions. This work does not give evidence for the hypothesis that MS and atopy, reflecting Th1 and Th2 polarization, respectively, are mutually exclusive. Further work, ideally with a matched control population, is indicated.

Adjuvants, Immunologic↗
PubMed2003

The relationship of brain and cervical cord volume to disability in clinical subtypes of multiple sclerosis: a three-dimensional MRI study.

OBJECTIVES: Brain and cervical cord volume is a potentially valuable index marker of irreversible pathological processes in multiple sclerosis (MS). Volume in both brain and cervical cord regions in the same patients has only been investigated in a small number of subjects. We aimed at measuring volume in different parts of the central nervous system, and its relationship with clinical measures, in relapsing-remitting (RR) and secondary progressive (SP) MS patients. MATERIAL AND METHODS: Conventional dual echo and three-dimensional (3-D) magnetization prepared rapid acquisition gradient echo imaging was performed on 97 (49 RR and 48 SP) MS patients, and on 31 age- and gender-matched healthy controls. The volumes of the supratentorial brain, lateral ventricles, brainstem, cerebellum and upper cervical cord (UCC) were determined on 3-D magnetic resonance imaging. RESULTS: RR MS patients had significantly smaller supratentorial brain (P=0.002) and larger lateral ventricles (P=0.047) compared with controls, but no differences were found for cerebellum, brainstem and UCC volumes. Significantly smaller supratentorial brain (P<0.0001), cerebellum (P=0.007), brainstem (P=0.0004) and UCC (P<0.0001) volumes, and larger lateral ventricles (P<0.0001) were observed in SP MS patients than in controls. In RR MS, T2-lesion volume correlated with supratentorial (r=-0.46, P=0.0009), lateral ventricular (r=0.65, P<0.0001), cerebellar (r=-0.42, P=0.003) and brainstem (r=-0.35, P=0.01) volumes, but not with UCC volume (r=-0.18, P=0.22). In SP MS, apart from lateral ventricular volume (r=0.52, P=0.0002), none of the estimated structural volumes correlated with T2-lesion volume. The UCC volume correlated with brainstem volume in both RR MS (r=0.35, P=0.016) and SP MS (r=0.38, P=0.007). Multiple regression analysis showed that supratentorial brain volume in RR group, and UCC volume in SP group, were single significant contributors (P=0.01 and 0.04, respectively) to the Expanded Disability Status Scale of all factors entered into the regression model. CONCLUSION: Atrophy is confined to the supratentorial compartment early in the disease course corresponding to the RR stage, but becomes more pronounced in the brain and cervical spinal cord in the SP phase. The estimate of cervical cord volume for SP MS is relevant to functional disability and may be helpful in monitoring MS evolution in the progressive form of disease.

Adult↗
PubMed2003

Spinal cord atrophy and disability in multiple sclerosis over four years: application of a reproducible automated technique in monitoring disease progression in a cohort of the interferon beta-1a (Rebif) treatment trial.

BACKGROUND: Pathology in the cervical spinal cord is considered an important cause of disability in multiple sclerosis. However, the majority of serial studies have failed to find a correlation between spinal cord atrophy and disability. OBJECTIVES: To use a highly reproducible and accurate method to quantify spinal cord area change on three dimensional magnetic resonance imaging and relate this to disability change in patients with multiple sclerosis. METHODS: 38 patients with multiple sclerosis (20 with the relapsing-remitting (RRMS) form and 18 with the secondary progressive (SPMS) form) were imaged at baseline and at months 6, 12, 18, and 48 during two treatment trials of the high dose subcutaneous thrice weekly interferon beta-1a (IFNbeta, Rebif). Thirty one healthy subjects were also imaged at baseline. Upper cervical cord area (UCCA) was measured using Sobel edge detection. RESULTS: The intraobserver coefficient of variation of the method was 0.42%. A significant reduction in UCCA was detected at month 6 in the placebo group (p = 0.04) and at month 12 for INFbeta (p = 0.03). The mean reduction of UCCA at month 48 was 5.7% for patients initially on placebo who received treatment at 24 months (RRMS) or at 36 months (SPMS), and 4.5% for those on IFNbeta throughout the study (p = 0.35). The change in UCCA was significantly correlated with change in the expanded disability status scale at month 12 (r = 0.4, p = 0.016), month 18 (r = 0.32, p = 0.05), and month 48 (r = 0.4, p = 0.016) in the total cohort. CONCLUSIONS: Despite the small number of patients studied and the possible confounding effects of interferon treatment, this study showed that edge detection is reproducible and sensitive to changes in spinal cord area, and that this change is related to changes in clinical disability. This suggests a role for measurement of spinal cord atrophy in monitoring disease progression and possible treatment effects in clinical trails.

Adult↗
PubMed2001

Interleukin 15 stimulates production of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by human peripheral blood mononuclear cells.

In peripheral blood mononuclear cells (PBMC), matrix metalloproteinase (MMP)-9 mediates the extravasation of immune cells and may be involved in tissue destruction during inflammation. We investigated the effect of the pro-inflammatory cytokines interleukin (IL-)12 and 15 on the secretion of MMP-9 in PBMC. IL-15, but not IL-12, induces MMP-9 in PBMC and in T cells. Moreover, the combination of IL-15 and IL-2 had an additive effect. In contrast, both IL-12 and IL-15 induced the release of tissue inhibitor of metalloproteinases (TIMP)-1. IL-15 led to a dose-dependent increase of the MMP-9/TIMP-1 ratio as a measure for increased proteolytic capacity. We conclude that IL-15 mediates its effects in inflammation in part through MMP-9.

Cells, Cultured↗
PubMed2001

Modulation of susceptibility and resistance to an autoimmune model of multiple sclerosis in prototypically susceptible and resistant strains by neutralization of interleukin-12 and interleukin-4, respectively.

Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is mediated by Th1 cells. The major Th1 inducer, IL-12, enhances EAE, while its blockade suppresses it. IL-4 suppresses EAE. Here, we determined IFN-gamma and IL-4 production by myelin basic protein-stimulated lymphocytes from prototypically EAE-susceptible SJL/J and EAE-resistant BALB/c mice, 9 days after immunization with spinal cord homogenate. While lymphocytes from SJL/J mice produce IFN-gamma and no IL-4, lymphocytes from BALB/c mice produce IL-4 and no IFN-gamma. Since early endogenous production of IL-12/IFN-gamma or IL-4 is linked to Th1 or Th2 responses, respectively, we determined whether neutralization of IL-12 or IL-4 at immunization modifies susceptibility or resistance to EAE. SJL/J mice given neutralizing anti-IL-12 mAb are protected from EAE. BALB/c mice given neutralizing anti-IL-4 mAb develop EAE, while those treated with control antibody remain resistant. These studies confirm the pivotal role of IL-12 in EAE development and show that endogenous IL-4 is important for determining the genetic resistance to EAE.

Animals↗
PubMed2001

Possible role of corticosteroids in nervous system plasticity: improvement in amblyopia after optic neuritis in the fellow eye treated with steroids.

OBJECTIVE: Amblyopia consists of reduced visual function in the absence of organic disease, caused by deficient visual stimulation, most commonly due to squint or refractive error. Amblyopia is thought to be reversible up until the age of approximately 8 years (critical period) and is usually treated with occlusion of the fellow eye. There is recent evidence for visual system plasticity extending beyond the critical period, supported by reports of improvement in visual acuity in the amblyopic eye after loss of vision in the contralateral eye. This suggests that the adult visual system exhibits sufficient plasticity to allow such improvement. We describe here improvement in visual acuity in three amblyopic patients after they received high-dose intravenous glucocorticoids for optic neuritis in the contralateral eye. METHODS: Clinical and neurological evaluation added. RESULTS: In all cases, the improvement was sustained, even after the recovery from the optic neuritis. CONCLUSIONS: Because steroids affect neural plasticity, we hypothesize that they facilitate and enhance visual improvement in amblyopia, a quality that may be tested in future controlled trials.

Adult↗
PubMed2000

Experimental allergic neuritis in the SJL/J mouse: induction of severe and reproducible disease with bovine peripheral nerve myelin and pertussis toxin with or without interleukin-12.

We report a reproducible model of experimental allergic neuritis (EAN) with severe clinical signs and consistent pathological features in mice. Pertussis toxin (PT) in the presence or absence of murine recombinant interleukin-12 (mrIL-12) was used as an adjuvant with bovine peripheral nerve myelin (BPNM) to induce clinical EAN in SJL/J mice. After immunization with a combination of BPNM in complete Freund's adjuvant (CFA) and PT, mice developed severe consistent signs of EAN. The additional treatment of immunized mice with mrIL-12 prolonged the course of EAN characterized by earlier clinical signs of the disease and delayed the recovery stage. Mice injected with BPNM and CFA without PT developed mild clinical signs. Histological examination of the caudae equinae and the sciatic nerves taken from mice with clinical signs of EAN during the recovery stage revealed severe demyelination, remyelination and remnants of mononuclear cell infiltration. Moderate to severe EAN can be induced in SJL/J mice by the injection of a combination of BPNM in CFA and PT. This model can provide a better understanding of mechanism of demyelination in infiltrating peripheral neuropathy.

Animals↗
PubMed2000

Murine macrophages stimulated with central and peripheral nervous system myelin or purified myelin proteins release inflammatory products.

Macrophage inflammatory products including tumor necrosis factor (TNF) and interleukin-12/p40 are implicated in demyelinating diseases such as multiple sclerosis (MS), Guillain-Barré syndrome, and animal models experimental autoimmune encephalomyelitis and neuritis. The macrophage product angiotensin converting enzyme (ACE) is released during inflammation. ACE can also be elevated in MS. We investigated the ability of central (CNS) and peripheral nervous system (PNS) myelin to stimulate TNF, interleukin-12, and ACE production by murine macrophages. Both CNS and PNS myelin and purified myelin basic protein and P2 protein induced release of these products. Direct stimulation by myelin may represent a mechanism of inducing release of macrophage products in inflammatory demyelination or neural injury.

Animals↗
PubMed2000

Glatiramer acetate (Copaxone) treatment in relapsing-remitting MS: quantitative MR assessment.

OBJECTIVE: To evaluate the efficacy of glatiramer acetate (GA, Copaxone; Teva Pharmaceutical Industries, Ltd., Petah Tiqva, Israel) by MRI-based measures in patients with relapsing-remitting (RR) MS. METHODS: Twenty-seven patients with clinically definite RR-MS were treated with either 20 mg of GA by daily subcutaneous self-injection (n = 14) or placebo (n = 13) for approximately 24 months. Axial dual-echo fast-spin-echo T2-weighted images and T1-weighted images before and after gadolinium (Gd) were acquired at 1.5 tesla and transferred into an image processing computer system. The main outcome measures were the number of Gd-enhanced T1 and T2 lesions and their volume as well as brain parenchyma volume. RESULTS: The values of age, disease duration, Expanded Disability Status Scale (EDSS) score, the number of T1- and T2-weighted lesions, and their volume were similar between GA- and placebo-receiving groups at the entry of this study. There was a decrease in the number of T1-enhanced lesions (p = 0.03) and a significant percent annual decrease of their volume in GA recipients compared with those of placebo recipients. There were no significant differences between changes in the two groups in the number of T2 lesions and their volume. The loss of brain tissue was significantly smaller in the GA group compared with that of the placebo group. CONCLUSIONS: These results show that GA treatment may decrease both lesion inflammation and the rate of brain atrophy in RR-MS.

Adult↗
PubMed2000

Long term azathioprine fails to prevent onset of multiple sclerosis: report of two cases.

Azathioprine is an immunosuppressive drug widely used in the treatment of chronic inflammatory diseases, including Multiple Sclerosis (MS). We report two patients who developed the first manifestations of clinically definite multiple sclerosis while on long term (3.5 and 10 years, respectively) treatment with azathioprine for Crohn's disease. Both patients developed the first MS symptoms during a quiescent phase of their inflammatory bowel disease. These cases show that long term azathioprine, while possibly maintaining inflammatory bowel disease under control, could not prevent the onset of MS. Multiple Sclerosis (2000) 6 362 - 363

Adult↗