Progression of optic neuritis to multiple sclerosis in the County of Split-Dalmatia, Croatia

The aim of this study was to determine the incidence of monosymptomatic optic neuritis (MON) and progression of MON to multiple sclerosis (MS) from the Mediterranean region of southern Europe in the County of Split-Dalmatia, Croatia during the 11 years period from 1991 to 2001. This study was made retrospectively on the 87 cases (59 female, aged 25.9 +/- 11.3 and 28 male aged 29.9 +/- 9.2) of MON, which were treated at the Department of Ophthalmology and Department of Neurology, Split, University Hospital, from January 1991 to December 2001. In each case the diagnosis was confirmed by a chart review and cases were ascribed to the data of admittance at hospital. The annual incidence of MON was 1.9 per 100,000 (95% CI, 0.4-3.5). The incidence among males was 1.2 (95% CI, 0-2.9) cases / 100,000 per year and 2.5 (95% CI, 0.1-4.9) among females. A significant seasonal variations in the incidence of MON was not found (chi2 = 6.81, p = 0.08). MS developed in 20 of 87 patients (22.9%) and median time was 25 (SE 8) months, (95% CI, 9-41) after the MON onset. After two years 12.6% of patients with MON developed MS, 20.6% after 5 years and 22.9% after 10 years. MS was slightly but not significantly more frequent in women than in men (chi2 = 0.72, p = 0.3). In conclusion, the progression of MON to MS in the County of Split-Dalmatia, Croatia was at a relatively moderate frequency.     

Epidemiology of monosymptomatic optic neuritis in Rijeka County, Croatia: meteorological aspects

In order to analyze the meteorological factors possibly influencing the monosymptomatic optic neuritis in Rijeka County, northwestern part of Croatia, retrospective analysis of all cases diagnosed in Rijeka County in period from 1977 to 2001, was done. Meteorological data on monthly and yearly temperature, humidity, insolation in Rijeka County were collected from Croatian Meteorological and Hydrological Service. In the observed period there were 173 cases of monosymptomatic optic neuritis, female/male ratio was 1.66, and overall incidence was 2.18/100,000 inhabitants. There was no correlation of incidence with average yearly and monthly temperature, humidity, insolation, or month of birth. This is the first study on meteorological factors and optic neuritis in Croatia.     

The incidence of stroke in Baranya county (east Croatia)

The aim of this retrospective study was to provide a survey of the incidence of stroke in Baranya, Croatia, on patients examined at Beli Manastir Health Center Department of Emergency from November 1, 1997 (the time of Baranya reintegration into the legal system of the Republic of Croatia after the war) till December 31, 2001. A total of 513 patients with symptoms of cerebrovascular diseases, or one patient every third day on an average, were examined. Total incidence of stroke was 16.09 per 10,000 population. The majority of patients were in the 61-80 age group with an incidence of 46.94/10,000 after the age of 60, 15-fold that was recorded in younger age groups. The most common risk factors recorded in examined group included hypertension, heart diseases, hyperlipidemia and diabetes mellitus. Total stroke mortality was 38.38%, whereas mortality in patients with hemorrhagic and ischemic stroke was 62.85% and 33.52%, respectively. The ratio of ischemic and hemorrhagic stroke in study subjects was 5:1, and in the causes of death 2.5:1. Out of 81 deceased stroke patients, 96.3% died within first 28 of admission. All of the patients with hemorrhagic stroke died within first 28 days, most within first 7 days (81.8%), whereas 94.9% of patients with ischemic stroke died within first 28 days.     

Measles-virus-specific IgG in optic neuritis and in multiple sclerosis after optic neuritis.

Measles-virus-specific IgG was measured in the serum of 100 patients who had presented with optic neuritis (ON) during 1960-74. When reviewed 41 of them were found to have developed definite symptoms and signs of multiple sclerosis (MS), their serum containing significantly higher titres of the antibody than sera from either the rest of the patients or a group of normal healthy controls. In a few patients from whom cerebrospinal fluid (CSF) was obtained in the acute phase of ON, titres of measles IgG in the serum was higher in those in whom the antibody was detected in the CSF than the serum of patients without CSF antibody.     

The electroretinogram in multiple sclerosis and demyelinating optic neuritis

The electroretinogram (ERG) to flashes of white light presented under photopic conditions and the pattern reversal visual evoked potentials (PR-VEPs) from both eyes were recorded from 14 patients with multiple sclerosis (MS) with monocular demyelinating optic neuritis (DON) and from 11 patients soon after presenting with monocular demyelinating optic neuritis alone. Fifteen and 10 normal subjects, matched for age and sex, were used as controls for each group of patients respectively. In the DON group of patients and controls the flicker following ERG (FF-ERG) to white flashes of light at 40 Hz was also recorded. Skin electrodes and averaging procedures were used for all the recordings. The PR-VEP elicited with stimulation of the affected eye was absent or abnormally delayed, and the amplitude of the ‘b’ wave of ERG of the affected eye was diminished in all patients. The ‘b’ wave latency, however, was similar in both affected and non-affected eyes and the controls. There was no difference in ‘a’ wave amplitude and latency between eyes of patients and normal subjects. The FF-ERG in 8 out of 10 patients with satisfactory recordings was diminished in the affected eye. These results provide neurophysiological evidence that retinal damage is not due to loss of myelin but is an early feature of demyelinating optic neuritis. This damage preferentially affects the retinal elements associated with the generation of the ‘b’ wave of the ERG, probably the glial cells of Müller.     

New actors in optic neuritis pathogenesis

The aim of the present report was to analyze the involvement of glutamate neurotoxicity in retinal ganglion cell loss and optic nerve damage induced by experimental optic neuritis. For this purpose, the authors used an optic neuritis model induced by immunisation with myelin oligodendrocyte glycoprotein (AON). The authors describe a correlation in the timing of retinal ganglion cell (RGC) loss with alterations in the optic nerve actin cytoskeleton dynamic, and visual dysfunction. In addition, they show that an intravitreal injection of glutamate mimics, and an NMDA receptor antagonist avoids the effect of pre-clinical AON on visual functions and RGC number, as well as on optic nerve actin cytoskeleton. Taken together, their results support that avoiding glutamate neurotoxicity could become a new therapeutic approach for optic neuritis treatment.

     

Calpain inhibitor attenuated optic nerve damage in acute optic neuritis in rats

Optic neuritis (ON), which is an acute inflammatory autoimmune demyelinating disease of the central nervous system (CNS), often occurs in multiple sclerosis (MS). ON is an early diagnostic sign in most MS patients caused by damage to the optic nerve leading to visual dysfunction. Various features of both MS and ON can be studied following induction of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in Lewis rats. Inflammation and cell death in the optic nerve, with subsequent damage to the retinal ganglion cells in the retina, are thought to correlate with visual dysfunction. Thus, characterizing the pathophysiological changes that lead to visual dysfunction in EAE animals may help develop novel targets for therapeutic intervention. We treated EAE animals with and without the calpain inhibitor calpeptin (CP). Our studies demonstrated that the Ca²⁺‐activated neutral protease calpain was upregulated in the optic nerve following induction of EAE at the onset of clinical signs (OCS) of the disease, and these changes were attenuated following treatment with CP. These reductions correlated with decreases in inflammation (cytokines, iNOS, COX‐2, and NF‐κB), and microgliosis (i.e. activated microglia). We observed that calpain inhibition reduced astrogliosis (reactive astroglia) and expression of aquaporin 4 (AQP4). The balance of Th1/Th2 cytokine production and also expression of the Th1‐related CCR5 and CXCR3 chemokine receptors influence many pathological processes and play both causative and protective roles in neuron damage. Our data indicated that CP suppressed cytokine imbalances. Also, Bax:Bcl‐2 ratio, production of tBid, PARP‐1, expression and activities of calpain and caspases, and internucleosomal DNA fragmentation were attenuated after treatment with CP. Our results demonstrated that CP decreased demyelination [loss of myelin basic protein (MBP)] and axonal damage [increase in dephosphorylated neurofilament protein (de‐NFP)], and also promoted intracellular neuroprotective pathways in optic nerve in EAE rats. Thus, these data suggest that calpain is involved in inflammatory as well as in neurodegenerative aspects of the disease and may be a promising target for treating ON in EAE and MS.     

Influence of antioxidant enzymes in reduction of optic disc edema in experimental optic neuritis

Acute experimental allergic optic neuritis was induced in 18 adult strain-13 guinea pigs. The animals were divided into three groups. The first group of six animals received intraperitoneal injections of saline, the second group received superoxide dismutase (SOD), and the third group received catalase, given daily, starting 1 week after encephalogenic myelin sensitization. Morphometric analysis of longitudinal histopathologic sections of the optic nerve head revealed that the animals treated with the antioxidant enzyme catalase had a statistically significant reduction of optic disc edema when compared to the saline-treated group. Although animals treated with SOD had less optic disc swelling than the saline-treated controls, the differences were not statistically significant. These results indicate that detoxification of hydrogen peroxide, released by invading inflammatory cells, can reduce the severity of axonal swelling within the optic nerve head.     

Bilateral optic neuritis in a child following Epstein-Barr virus infection

A rare case of bilateral optic neuritis is presented in a child with no light perception. Ophthalmic examination revealed dilated pupils without reaction to the light, swollen optic discs with small peripapillary hemorrhages in both eyes. Serology revealed evidence of recent Epstein-Barr virus infection. After treatment with high dose of corticosteroid visual acuity gradually improved. After four months visual acuity was normal despite complete pallor of the optic disc. Ebstein-Barr virus infection should be considered in the differential diagnosis of bilateral optic neuritis in a child with severe bilateral visual loss.     

The pattern electroretinogram: N95 amplitudes in normal subjects and optic neuritis patients

Recent work has suggested that the N95 peak of the transient pattern electroretinogram (PERG) may be a more sensitve indicator of the late stages of retinal function prior to optic nerve activation than the P50 peak. In the report, we show that a new measure of N95 amplitude, based on digital filtering methods to identify a non-linear baseline measurement, greatly reduced the amplitude variation in a population of 50 normal subjects when compared with two other plausible measures. We then used that new measure to follow the time course of N95 amplitudes in 12 optic neuritis patients. It was found that mintenance of a normal N95 amplitude at 6 months after onset of optic neuritis was always associated with excellent clinical recovery as measured by visual fields, acuity, presence or absence of an afferent pupil and optic atrophy, and contrast sensitivity (CS). Loss of N95 amplitude to below laboratory limits of normal was associated with abnormalities in these indicators of visual function. This study supports the idea that the N95 peak represents retinal ganglion cell function.     

The temporal frequency response function of pattern ERG and VEP: changes in optic neuritis

Steady-state pattern electroretinograms (PERGs) and visual evoked potentials (VEPs) in response to sinusoidal gratings (2 c/deg), sinusoidally counterphased at closely spaced temporal frequencies (TFs) between 4 and 28 Hz, were recorded from 11 patients with unilateral optic neuritis (ON; 11 affected eyes and 10 healthy fellow eyes) and 7 age-matched normal subjects (7 eyes). Amplitude and phase of responses' second harmonics were measured. Responses' apparent latencies were estimated from the rate at which phase lagged with TF. When compared to control values, mean PERG and VEP amplitudes of ON eyes were reduced (by about 0.4 log units) at both low (5–10 Hz) and high (16–20 Hz) TFs. Mean PERG amplitudes of fellow eyes were selectively reduced at low TFs (by about 0.3 log units). Mean PERG apparent latencies of both ON and fellow eyes were delayed (by 15 and 9 ms, respectively). Mean VEP apparent latency of ON eyes was delayed at both low and high TFs (by 24 and 30 ms, respectively), while that of fellow eyes was selectively delayed at high TFs (by 28 ms). The results in ON eyes indicate non-selective abnormalities of PERG and VEP generators responding at both low and high TFs. VEP TF losses may be in part accounted for by corresponding PERG losses. In the fellow eyes of patients, more selective PERG and VEP TF abnormalities may suggest differential impairment of retinal and postretinal subsystems responding better to low and high TFs (i.e. parvo-and magnocellular streams).     

Treatmenf of optic neuritis by retrobulbar injection of triamcinolone.

In a single-blind controlled clinical trial patients with optic neuritis caused by demyelination were given a single retrobulbar injection of triamcinolone. Though the treated group showed a trend towards more rapid recovery of vision than the controls, there was no significant difference in visual acuity, colour vision, or visual fields during the first six months after treatment. We conclude that routine use of corticosteroids is not justified in unilateral optic neuritis when vision in the other eye is good. Shortening the period of visual disability in bilateral disease or unilateral disease when vision in the other eye is poor, however, may be justifiable.     

Use of pattern electroretinography to differentiate acute optic neuritis from acute anterior ischemic optic neuropathy

The transient pattern electroretinogram (PERG) was recorded from 16 patients with acute neuritis and from 13 patients with acute non-arteritic ischemic optic neuropathy (AION). All patients were tested within 35 days from the the onset of visual symptoms and all had significant central visual field abnormalities in their affected eyes as quantified by automated perimetry. Analysis of the PERGs showed that the amplitude of the N95 peak was abnormally reduced for each eye affected with AION while it remained normal in optic neuritis. No significant alteration in P50 amplitude was observed in either condition. The loss of N95 amplitude in AION was highly correlated with the average depth of visual field loss (in decibels) within a radius of 10° of fixation. These results suggest that PERG could be used early in the course of optic neuropathy to distinguish optic neuritis from AION in those cases for which the diagnosis is still uncertain after the clinical examination.     

A putative role for calpain in demyelination associated with optic neuritis

Calcium activated neutral proteinase (calpain) is an endopeptidase present in the central nervous system which degrades myelin proteins. To examine the role of calpain in demyelination associated with optic neuritis, immunocytochemical expression of calpain was evaluated in Lewis rats with experimental optic neuritis. Calpain expression was increased in activated microglia, infiltrating macrophages, activated T cells, and reactive astrocytes in experimental optic neuritis compared to controls. Calpain activity and translational expression were also examined by Western blotting studies measuring the extent of myelin protein degradation, calpain-specific fodrin proteolysis, axonal neurofilament degradation, and calpain proenzyme content. Results showed myelin associated glycoprotein and 68 kD neurofilament protein levels were significantly decreased while calpain translational expression and calpain-autolyzed fodrin levels were significantly increased in experimental optic neuritis compared to controls. Thus, increased activity and translational expression of calpain in optic neuritis may be integral to the pathogenesis of this disorder.     

Visual field defects of optic neuritis in neuromyelitis optica compared with multiple sclerosis

Background

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that predominantly affects the optic nerves and the spinal cord, and is possibly mediated by an immune mechanism distinct from that of multiple sclerosis (MS). Central scotoma is recognized as a characteristic visual field defect pattern of optic neuritis (ON), however, the differing pathogenic mechanisms of NMO and MS may result in different patterns of visual field defects for ON.

Methods

Medical records of 15 patients with NMO and 20 patients with MS having ON were retrospectively analyzed. A thorough systemic and neurological examination was performed for evaluating ON. The total number of relapses of ON and visual fields was investigated. Visual fields were obtained by Goldmann perimeter with each ON relapse.

Results

All MS patients experienced central scotoma, with 90% of them showing central scotoma with every ON relapse. However, 53% of NMO patients showed central scotoma with every ON relapse (p = 0.022), and the remaining 47% of patients experienced non-central scotoma (altitudinal, quadrant, three quadrant, hemianopia, and bitemporal hemianopia). Thirteen percent of NMO patients did not experience central scotoma during their disease course. Altitudinal hemianopia was the most frequent non-central scotoma pattern in NMO.

Conclusions

NMO patients showed higher incidence of non-central scotoma than MS, and altitudinal hemianopia may be characteristic of ON occurring in NMO. As altitudinal hemianopia is highly characteristic of ischemic optic neuropathy, we suggest that an ischemic mechanism mediated by anti-aquaporin-4 antibody may play a role in ON in NMO patients.

     

Five-year cumulative incidence of obesity in adults in Croatia: the CroHort study

The objective of this paper was to evaluate the 5-year incidence of obesity on a sample of 3229 adults and investigate the potential effect of several sociodemographic and lifestyle habits on weight change and obesity incidence in these individuals. The average annual rate of increase in the prevalence of obese adults between 2003 and 2008 was 10.60% for men and 11.08% for women. Analysis showed that development of obesity in 5-year period in women in Croatia is significantly positively associated with frequent consumption of "hidden" fats of animal origin and significantly negative with each higher education level. No significant predictor of obesity has been found in men. Obesity remains a serious health problem for the Croatian population; the alarming rates of excess body weight continue to increase. Preventive measures should urgently be undertaken.