Impact of Helicobacter pylori on multiple sclerosis-related clinically isolated syndrome.

OBJECTIVES: There are no data regarding the relationship between Helicobacter pylori infection (Hp-I) and clinically isolated syndrome (CIS) suggestive of multiple sclerosis. The purpose of this pilot study was to investigate the association between active Hp-I, confirmed by histology, and CIS and to evaluate the impact of Hp eradication on the CIS clinical course. MATERIAL AND METHODS: We conducted a study on 48 patients with CIS and 20 matched controls. At baseline, apart from histology, serum anti-Hp-specific IgG titer, inflammatory mediators, and HLA-A, HLA-B, HLA-DR genetic polymorphisms were estimated. Hp-positive patients received standard triple eradication regimen, and all patients were followed up for 2 years. RESULTS: The prevalence of Hp-I was significantly higher in patients with CIS (43/48, 89.6%) than in control (10/20, 50%) (P < 0.001, OR: 8.6, 95% CI: 2.4-30.8). When compared with controls, patients with CIS also showed significantly higher serum anti-Hp IgG titer and HLA-A26, HLA-A30, and HLA-B57 frequencies. Hp-positive patients also showed higher serum concentrations of inflammatory cytokines and homocysteine. At 2-year clinical endpoint, in the subgroup of CIS patients with successful Hp eradication, the number of patients who presented with a second episode was significantly lower accompanied by significant improvement in mean Expanded Disability Status Scale score. CONCLUSIONS: Hp-I seems more frequent in a Greek CIS cohort and its eradication might delay CIS progression, suggesting a possible link between Hp-I and CIS.

Polyautoimmunity in a Greek cohort of multiple sclerosis.

OBJECTIVES: The aim of this study was to assess the existence of polyautoimmunity in a Greek cohort of multiple sclerosis (MS), particularly multiple autoimmune syndrome (MAS), i.e., the presence of three or more distinct autoimmune disorders (ADs) in the same individual. METHODS: Cross-sectional control study. RESULTS: The overall prevalence of polyautoimmunity in 2140 MS patients (female to male ratio: 2.1:1) was 8.3% (vs 6.07% in 1580 matched control participants, P = 0.008) mainly due to differences in autoimmune thyroid disorders (AITD) and vitiligo. The prevalence of MAS was 1.0%. The most frequent diseases encountered in MS were organ-specific ADs. There was no statistical difference in the total rates of ADs between female and male MS patients. There were higher rates of AITD in women (P = 0.004) and higher rates of iritis (P = 0.039) and ankylosing spondylitis (P = 0.003) in men. MS was diagnosed in the same year with AD in 7.4% of patients with additional ADs, earlier than AD in 42.0% and later than AD in 50.6%. CONCLUSION: Polyautoimmunity and particularly MAS occur more frequently in MS patients than in control participants indicating that MS may be part of a generalized susceptibility to autoimmunity. Therefore, polyautoimmunity may be implicated in the etiopathogenesis of MS-related ADs, with a potential impact on relative therapeutic strategies.

The impact of oxaliplatin-based chemotherapy for colorectal cancer on the autonomous nervous system.

BACKGROUND: The oxaliplatin (ΟΧΑ)-based regimens FOLFOX and XELOX can cause peripheral neuropathy. It is unknown if ΟΧΑ, alone or in combination regimens, affects the Autonomous Nervous System (ANS). Accordingly, we evaluated the impact of ΟΧΑ-based chemotherapy on the ANS. METHODS: We enrolled 36 patients with colorectal cancer, treated with adjuvant mFOLFOX6 or XELOX chemotherapy, and 22 healthy volunteers. For the assessment of ANS function, participants completed a questionnaire and underwent neurophysiological examination at three time points (baseline, 3-4 months and 6-8 months after the first chemotherapy cycle). ANS testing included assessment of the adrenergic cardiovascular function (orthostatic hypotension-OH), parasympathetic heart innervation (ratio 30/15) and Sympathetic Skin Response (SSR). RESULTS: The values of the 30/15 ratio were significantly reduced at the two time point assessments compared to baseline (Wilcoxon signed ranks test, both P < 0.001), while patients had more often diastolic OH at the 6-8 month evaluation compared to baseline (P = 0.039). In contrast, SSR was not affected. The incidence of positive responses in the questionnaire assessing the subjective impact of symptoms attributable to ANS dysfunction was higher at the two time points compared to baseline (P = 0.036 and P = 0.020). CONCLUSIONS: Oxaliplatin-based chemotherapy is associated with significant effects on the adrenergic cardiovascular reaction and the parasympathetic heart innervation, whereas SSR remains untouched.

Gastrointestinal immune system and brain dialogue implicated in neuroinflammatory and neurodegenerative diseases.

A common characteristic of the central nervous system (CNS) neurodegenerative disorders is neuroinflammation, marked by augmented numbers of activated and primed microglia, increased inflammatory cytokines and decreased anti-inflammatory molecules. CNS neuroinflammation is a critical component in the progression of several neurodegenerative diseases which sensitize the brain to produce an exaggerated response to immune stimuli in the periphery. Neuroinflammation might initiate from the periphery and peripheral conditions through disrupted blood-brain barrier powerfully influence various brain pathologies. Gastrointestinal tract (GIT) represents a vulnerable area through which pathogens influence the brain and induce CNS neuroinflammation. The pathogens may access the CNS through blood, the nasal olfactory pathways and the GIT. Potential GI pathogens, such as Helicobacter pylori, induce humoral and cellular immune responses that, owing to the sharing of homologous epitopes (molecular mimicry), cross-react with CNS components thereby contributing and possibly perpetuating neural tissue damage. GIT is strictly connected to the CNS and a bi-directional communication exists between them. The brain is involved in regulating the immune and gut system. Conversely, limited attention has been paid on the GIT role in the development and regulation of the CNS autoimmune diseases. The GIT is the primary immune organ with specialized immunoregulatory and anti-inflammatory functions, represented by the gastrointestinal immune system (GIS). This review focuses on the potential GIS and brain dialogue implicated in neurodegenerative diseases. Gaining a better understanding of the relationship between GIS and CNS could provide an insight on the pathogenesis and therapeutic strategies of these disorders.

Comparative bioequivalence study of two isotretinoin soft gel capsule formulations in healthy male volunteers.

OBJECTIVE: To assess the bioequivalence of 2 oral isotretinoin (20 mg) soft gel capsule formulations. The reference preparation was Roaccutan/Roche while the test preparation was A-Cnotren/Pharmaten, Athens, Greece. SUBJECTS, MATERIAL AND METHODS: The study was an open, randomized, 2-period, 2-sequence, 2-treatment crossover, involving 38 healthy male volunteer subjects. All volunteers completed the study. Isotretinoin plasma concentrations were measured by a fully validated HPLC method. Special care was taken through the collection and analysis of the samples due to instability of isotretinoin to light and temperature. Pharmacokinetic parameters used to assess bioequivalence were AUC(0-last), AUC(0-infinity) for the extent of absorption and Cmax and Tmax for the rate of absorption. Statistical evaluation of Cmax, AUC(0-last), AUC(0-infinity) was done after semi-logarithmic transformation by 2-way analysis of variance (ANOVA). Tmax values were tested using the distribution-free Hodges-Lehman interval. RESULTS: The parametric 90% confidence intervals for ratio T/R ranged from 95.20-103.20% (point estimate 99.10%) for AUC(0-last), 94.57-102.30% (point estimate 98.36%) for AUC(0-infinity) and 94.81-102.90% (point estimate 98.77%) for Cmax, respectively. Based on the results of Tmax, k(el) and t(1/2), too, there were no statistically significant differences. CONCLUSION: As a result, the 2 isotretinoin preparations in accordance with the European Union bioequivalence requirements, are equivalent with respect to rate and extent of absorption.

Reliability, validity and psychometric properties of the Greek translation of the Major Depression Inventory.

BACKGROUND: The Major Depression Inventory (MDI) is a brief self-rating scale for the assessment of depression. It is reported to be valid because it is based on the universe of symptoms of DSM-IV and ICD-10 depression. The aim of the current preliminary study was to assess the reliability, validity and psychometric properties of the Greek translation of the MDI. METHODS: 30 depressed patients of mean age 23.41 (+/- 5.77) years, and 68 controls patients of mean age 25.08 (+/- 11.42) years, entered the study. In 18 of them, the instrument was re-applied 1-2 days later and the Translation and Back Translation made. Clinical diagnosis was reached with the use of the SCAN v.2.0 and the International Personality Disorders Examination (IPDE). The Center for Epidemiological Studies-Depression (CES-D) and the Zung Depression Rating Scale (ZDRS) were applied for cross-validation purposes. Statistical analysis included ANOVA, the Spearman Product Moment Correlation Coefficient, Principal Components Analysis and the calculation of Cronbach's alpha. RESULTS: Sensitivity and specificity were 0.86 and 0.94, respectively, at 26/27. Cronbach's alpha for the total scale was equal to 0.89. The Spearman's rho between MDI and CES-D was 0.86 and between MDI and ZDRS was 0.76. The factor analysis revealed two factors but the first accounted for 54% of variance while the second only for 9%. The test-retest reliability was excellent (Spearman's rho between 0.53 and 0.96 for individual items and 0.89 for total score). CONCLUSION: The current study provided preliminary evidence concerning the reliability and validity of the Greek translation of the MDI. Its properties are similar to those reported in the international literature, but further research is necessary.

Neurophysiological investigation of cervical spondylosis.

The difficulties in diagnosing spinal cord lesions due to the cervical spondylosis is well-known in clinical neurology. In order to investigate the contribution of various neurophysiological examinations in the diagnosis in cervical spondylosis, we examined 70 patients suffering from cervical spondylosis, with peripheral nerve conduction studies, F-wave from the upper limb and electromyography from the corresponding muscles, as well as somatosensory evoked potentials (SEPs) from upper and lower limbs. Patients were separated into four groups: 20 patients had cervical spondylosis symptoms only; 15 patients had symptoms and signs of spinal root involvement; 15 patients had symptoms and signs of myelopathy; and 20 patients had symptoms and signs of both myelopathy and spinal root involvement. A group of 20 normal controls was also studied. In all groups of patients SEPs were the most sensitive electrophysiological study. Low-amplitude N13 and increased conduction time of N9-N13 and central conduction N13-N19 and LP-P27 were the most common finding in SSEP testing. SEPs were affected in many cases without CT-MRI findings of spinal cord pressure. From the above findings, SEPs proved to be the most sensitive diagnostic investigation in cervical spondylosis.

The value of neurophysiological and MRI assessment in demyelinating optic neuritis (DON).

PURPOSE: To study, by neurophysiological means, the possible involvement of the retina, in demyelinating optic neuritis (DON). MATERIAL AND METHODS: Thirty-five patients fulfilling strict criteria of unilateral DON were investigated with a battery of neurophysiological tests and MRI within 3 weeks of the onset of their symptoms. Flash-ERG (F-ERG) in photopic conditions, Flash-VEPs and PR-VEPs were recorded. MRI of the brain and the optic nerve were performed. RESULTS: The amplitude of b-wave of F-ERG in photopic conditions was statistically significantly lower in the affected eye (p < 0.001) compared to normal controls, whereas in the unaffected eye, it was also statistically significantly lower than normal controls (p < 0.01). All patients had statistically significant prolongation of P100 latency in PR-VEPs of the affected eye (p < 0.001) in comparison to normal controls. The P100 wave of the unaffected eye was also delayed (p < 0.01). In MRI, Gd-DTPA enhancement was observed in 7 symptomatic nerves with only minimal enhancement of the optic nerve between optic chiasm and optic canal, whereas 11 patients were presented with intracranial associated plaques. Five of the above patients had optic nerve enhancement and diffused demyelinating findings simultaneously. CONCLUSION: These results are a neurophysiological indication of involvement of the retina in DON, probably of vascular origin.

Dermatomal SEPs--a complementary study in evaluating patients with lumbosacral disc prolapse.

We investigated the value of Dermatomal Somatosensory Evoked Potentials in 24 patients with unilateral radiculopathy due to lumbosacral disk prolapse. All patients had clinical signs and symptoms of disk prolapse and positive findings on neuroradiologic testing. We assessed the latency and the amplitude of the first positive waveform of Dermatomal SEPs, as well as conducting peripheral nerve conduction studies and electromyography. Our studies showed a clear correlation of Dermatomal SEP abnormalities and radiculopathy in up to 83.3% of subjects studied. Use of electromyography testing provided this correlation in about 62.5% of the same subjects. On the basis of these results, we propose that Dermatomal SEPs have value in complementing the routine electrophysiological testing of the patients with radiculopathy and provide a sensitive non-invasive technique for defining the level of disk prolapse.