An in vivo confocal microscopy study of corneal changes in patients with systemic sclerosis.

To investigate corneal microstructure of systemic sclerosis (SSc) patients using in vivo confocal microscopy (IVCM). 33 patients with SSc and 30 age-matched healthy subjects were recruited. All participants underwent comprehensive ophthalmic examination including IVCM (Heidelberg Retina Tomograph III, Heidelberg Engineering GmbH, Heidelberg, Germany) and ocular surface evaluation. Subbasal nerve plexus morphology was investigated using automated software analysis (ACCMetrics V3; University of Manchester, Manchester, UK). Keratocyte cell densities in the anterior stroma were significantly lower in patients with SSc compared to controls (P < 0.0001). In 7 SSc patients no keratocyte nuclei were identified in the anterior stroma and in most patients scattered hyperreflective punctate material were observed in the anterior stroma. Significantly lower subbasal nerve fiber parameters were found in patients with SSc compared to healthy subjects (P < 0.05). There were no significant correlations between the duration of SSc and any of the corneal cell density values. Tear break-up time values (4.82 ± 3.15 s) and Ocular Surface Disease Index scores (33.27 ± 30.11) were abnormal, Schirmer values (6.78 ± 5.82 mm) were borderline in SSc patients. In SSc, corneal morphological changes and accumulation of punctate material in the stroma was detected with confocal microscopy. Severe ocular surface disease was observed in SSc patients with significant impairment in subbasal nerve plexus morphology resembling peripheral neuropathy.

A Wide Spectrum of Ocular Manifestations Signify Patients with Systemic Sclerosis.

Objectives: Systemic sclerosis (SSc) is a rare, chronic connective tissue disease involving multiple organ systems, including the eye. We evaluated the detailed clinical ocular manifestations of outpatients with SSc.Methods: Demographics, disease duration and subtype, nailfold capillaroscopy (NFC) patterns and laboratory parameters encompassing the autoantibody profile of 51 SSc patients were evaluated, and a general ocular examination was performed for each participant.Results: Twenty-nine patients (56.86%) had eyelid skin alterations, 26 (50.98%) had retinal abnormalities, 26 (50.98%) had cataracts, 8 (15.69%) had conjunctival changes, 7 (13.73%) had iris abnormalities, 33 (64.71%) suffered from dry eye disease (DED), and 11 (21.57%) suffered from glaucoma. Significant positive correlations were found between NFC data and both tear breakup time and Ocular Surface Disease Index test values.Conclusions: Eyelid skin abnormalities, DED and retinal abnormalities are among the most common SSc-related ocular involvements. Diverse ophthalmic findings are attributed to the heterogeneity of SSc.

Anterior segment parameters associated with extramuscular manifestations in polymyositis and dermatomyositis.

AIM: To evaluate detailed anterior segment parameters of patients with idiopathic inflammatory myopathies (IIM), including polymyositis (PM), and dermatomyositis (DM), and to clarify the associations between these data and clinical variables of IIM. METHODS: Totally 57 PM, 41 DM patients and 62 controls were enrolled in this cross-sectional, observational, case-control study. All study participants underwent Pentacam evaluation. Laboratory investigations consisted of different antibody assays, while extramuscular clinical assessments included Raynaud's phenomenon, dysphagia, interstitial lung disease, arthritis/arthralgia, and weight loss. Objective signs and subjective symptoms of dry eye disease (DED) were also evaluated. RESULTS: All pachymetric parameters [center, apex, thinnest and maximal keratometry (Kmax)] and corneal volume (CV) of both sides of PM patients proved to be significantly lower. Some pachymetric data were also noticed as significantly decreased compared to those of controls. Several significant differences were traced between anterior segment values and extramuscular manifestations of myositis, largely in case of arthritis/arthralgia and weight loss, whereas associations between anterior segment parameters and antibodies were weak. Objective clinical tests of DED were also significantly decreased in IIM patients. CONCLUSION: The results suggest that all IIM patients have thinner corneas compared with those of controls, and decreased corneal parameters are significantly associated with the occurrence of some extramuscular manifestations. In addition, IIM patients tend to develop objective signs of DED.

Corneal Involvement of Patients with Polymyositis and Dermatomyositis.

Purpose: To evaluate corneal parameters in patients with polymyositis (PM) and dermatomyositis (DM) and compare them with those of healthy controls.Methods: A total of 43 PM and 32 DM patients and 93 controls were enrolled in this cross-sectional, observational, case-control study. Corneal parameters were evaluated by Pentacam. Objective clinical tests of dry eye disease (DED) were also performed.Results: All pachymetric measurements and corneal volumes (CVs) proved to be significantly lower both in PM and DM patients. The values of DM patients were closer to control values than those of the PM patients. For tear break-up time and Schirmer-I test values significant differences were observed between patients and controls, with values decreased both in PM and DM patients.Conclusions: PM patients rather than DM patients tend to develop thinner and low-volume corneas as compared to controls. Additionally, a high prevalence of DED among both PM and DM patients was also detected.

Corneal Manifestations of Inflammatory Bowel Disease.

Purpose: To evaluate detailed corneal parameters of inflammatory bowel disease (IBD) patients, including Crohn's disease (CD) and ulcerative colitis (UC) patients, and to assess associations between anterior segment values and other clinical variables.Methods: This prospective cross-sectional case-control study at a tertiary referral center included 30 CD patients, 36 UC patients and 80 age- and gender-matched controls with no ocular symptoms or ocular surface disorders. All study participants underwent a comprehensive ophthalmological evaluation with special interest in dry eye disease (DED). Corneal parameters were evaluated by Pentacam.Results: The mean age of CD patients, UC patients, and controls was 45.80 ± 11.55 years, 52.00 ± 16.05, and 50.68 ± 14.62, respectively. The average disease duration was 12.72 ± 5.83 years for CD patients and 15.94 ± 10.09 years for UC patients. All pachymetric (center, apex and thinnest) and corneal volume (CV) measurements were significantly decreased, while anterior chamber angle width (ACA) values were significantly increased on both sides in all IBD patients compared to those in controls (p < .05). In addition, several anterior segment parameters were altered unilaterally in CD or UC patients. Negative correlations were found between corneal parameters and Schirmer I test values.Conclusions: Our investigations suggest that IBD patients have thinner corneas compared to that of controls. The coexistence of reduced tear quantity seems to have an additional impact on the thinning of the cornea in IBD patients. Early recognition of corneal impairments, a possible extraintestinal manifestation of IBD, should be included in the disease checkup to reduce vision-threatening developments.

Corneal Manifestations of Systemic Sclerosis.

Purpose: Corneal involvement in systemic sclerosis (SSc) is rare, but due to rich collagen composition cornea is especially vulnerable to connective tissue diseases. Therefore, our aim was to evaluate corneal parameters of SSc patients. Methods: The study included 32 SSc patients and 39 control subjects with no ocular symptoms or ocular surface disorders. All study participants underwent Pentacam evaluation and objective signs of dry eye disease (DED), and clinical parameters were evaluated. Results: All pachymetric values, most of the corneal front surface, corneal volume, as well as anterior chamber depth measurements were significantly lower in the SSc group than in the control group (p < 0.05). Significant negative correlation was found between corneal parameters and age on the one hand, and disease duration on the other. Conclusions: Early recognition of corneal impairment, a possible extraintestinal manifestation of SSc, should be included in the check-up of the disease in order to reduce sight-threatening complications.

[Neurological and psychiatric manifestations of systemic lupus erythematosus and antiphospholipid syndrome]. / A szisztémás lupus erythematosus és az antifoszfolipid-szindróma neurológiai és pszichiátriai szövodményei.

Neurological or psychiatric symptoms are present in 60% of the cases with systemic lupus erythematosus. Direct lesions of nervous system are associated with the presence of antibodies, vasculitis, thrombosis and impairments mediated by cytokines. Damages caused by injuries of other organs or those due to therapy are known as indirect causes. In the complex pathogenesis the primary cause is neuronal dysfunction mediated by autoantibodies, vasculopathia and coagulopathia. Until now, more than 20 antibodies have been identified in association with damages of the nervous system. These antibodies may impair neurons or astrocytes and may promote thrombotic processes in vessels of the brain. Activation of endothelial cells and disturbance of blood-brain barrier are also pathogenic factors. In patients with systemic lupus erythematosus the most frequent psychiatric manifestations are organic psychosyndrome, particularly deterioration of cognitive functions, and depression, while the most common neurological syndromes are epilepsy and ischemic stroke. In the pathogenesis of antiphospholipid syndrome ß2-glycoprotein I plays the most important role; binding to its antibody the complex may interact with cells and modify haemostatic actions. The most frequent neurological manifestations of antiphospholipid syndrome are headache and ischemic stroke.

[Neurological and psychiatric aspects of some gastrointestinal diseases]. / Néhány gastrointestinalis kórkép neurológiai és pszichiátriai vonatkozása.

The gastrointestinal tract is controlled by the independent enteric nervous system. It is also closely connected to the central nervous system, and bi-directional communication exists between them. The communication involves neural pathways as well as immune and endocrine mechanisms. The brain-gut axis plays a prominent role in the modulation of gut functions. Signals from different sources (e.g. sound, sight, smell, somatic and visceral sensations, pain) reach the brain. These inputs are modified by memory, cognition and affective mechanisms and integrated within the neural circuits of the central nervous system, spinal cord, autonomic and enteral nervous systems. These inputs can have physiologic effects, such as changes in motility, secretion, immune function, and blood flow to the gastrointestinal tract. One of the most important neurotransmitters is serotonin that plays a key role in the pathogenesis of the most common chronic functional gastrointestinal disorder: the irritable bowel syndrome. It is a biopsychosocial disease, resulting from the dysregulation of the brain-gut axis. Endogenous pain facilitation rather than inhibition, pathologic gradation of visceral perception and reduced threshold for pain are all evident in these patients. Abuse history is common in their anamnesis. Exaggerated conscientiousness, perfectionism, oversensitivity, feeling of deficiency in effectiveness, and higher demand for social parity, neuroticism and alexithymia have been detected among their constant personality features. Females are also characterized by gender role conflict and low assertiveness. Antidepressants and psychotherapy have important roles in their treatment. Also patients with inflammatory bowel disease are characterized by neuroticism and alexithymia and altered mother-child attachment is often described in their anamnesis. Autonomic neuropathy is a frequent and early neurological complication. Reflux disease and obstructive sleep apnea mutually generate each other and their severities significantly correlate. In the celiac disease the most common neurological manifestations are ataxia, peripheral neuropathy and myopathy. Up to 85% of patients with histologically proven coeliac disease have no gastrointestinal symptoms; consequently, measurement of antigliadin antibody titre is therefore vital in all cases of idiopathic ataxia. Complete resolution of neurological symptoms is the result of gluten-free diet.

[Cerebral complications of diabetes mellitus]. / A diabetes mellitus cerebrális szövôdményei.

According to WHO data more than 180 million people suffer from diabetes mellitus worldwide and this number could double within 15 years. Normal function of the brain is dependent on continuous supply of glucose. In hypoglycemia, production of counterregulatory hormones (glucagon, epinephrine, growth hormone, and cortisol) increases, the sympathetic system becomes stimulated, and features of neuroglycopenia appear in order to save the homeostasis. Hypoglycemia is an alarming, actually life threatening condition, but the exposure to chronic hyperglycemia has a more detrimental effect on the brain than recurrent exposure to severe hypoglycemia. The active neural response to hyperglycemia induces changes in gene expression and function. The first steps against hyperosmolality are initially adaptive, but later hyperactivation of the hypothalamic magnocellular neurosecretory cells leads to their structural damage. Changes in hippocampal gene transcription are partially implicated in the deterioration of declarative memory. Neurologically passive shunting of excess glucose through alternative cellular metabolic pathways induces atherogenic, vascular lesions, free radicals, leukoencephalopathy and atrophy of the brain and thus leading to cognitive deficits. In physiological conditions insulin has neuroprotective effect. However, insulin resistance in the central nervous system correlates with insulin resistance in the periphery. Loss of responsiveness to insulin could render neurons more susceptible to neurotoxic insults, the protective effect of insulin diminishes, and apoptosis, neurodegeneration and the resultant cognitive decline are all increased in insulin-resistant patients. Some unclear relations appear between diabetes mellitus and Alzheimer's disease. Diabetic patients with APOE-4 gene have an increased risk for Alzheimer's disease. Prevalence of depression is higher in patients with diabetes mellitus and in turn, depression is a risk factor for diabetes mellitus. Simultaneous presence of depression and diabetes mellitus tends to worsen the course of both.

[Neurological and psychiatric aspects of some endocrine diseases. The role of neurosteroids and neuroactive steroids]. / Néhány endokrin betegség neurológiai és pszichiátriai vonatkozása. neuroaktív szteroidok és neuroszteroidok.

Regardless of their origin, neuroactive steroids are capable of modifying neural activities by modulating different types of membrane receptors. Neurosteroids are synthesized de novo in neurones and glia. Steroidogenic enzymes are found in the central nervous system. Classical steroid receptors are localized in the cytoplasm, they exert regulatory actions on the genome, and their activation causes medium- and long-term effects. Non-classical receptors are located within the membrane and act as mediators of short-term effects. Other important players are co-repressors and co-activators that can interfere with or enhance the activity of steroid receptors. Beyond their function in stress, corticosteroids play a very important role in fear, anxiety, and memory functions. Patients with Cushing's syndrome frequently develop mood disorder, reversible brain atrophy with transient memory loss, rarely delirium or psychosis. Well-known peripheral symptom is steroidal myopathy. In patients with Addison's disease the main signs are weakness of muscles, lack of energy, decreased mental functions and reduced quality of life. Estrogen and progesterone have their own respective hormone receptors, whereas allopregnanolone acts via the GABA receptors. These hormones have significant role in the development of brain, the architecture of neural circuits and dendrites, density of axonal connections, and the number of neurons. They influence maturation, neuroprotection, seizures, cognitive functions, mood, anxiety, pain, and restitution of peripheral nerves. Androgens also affect cognitive functions, pain, anxiety, mood, and additionally aggression.

[Some neurological and psychiatric complications of the disorders of the hypothalamo-hypophyseal system]. / Néhány endokrin betegség neurológiai és pszichiátriai vonatkozása: hypothalamus-hypophysis rendszer.

Connection between the central nervous system and the endocrine system is extremely complex. The hypothalamus serves as a crucial centre for the integration and coordination of autonomic functions by neuronal and hormonal pathways. It plays a central role in the homeostatic regulation of internal physiological conditions. It controls growth and reproduction, stress reactions, and determines rhythmicity, periodicity and timing of physiological processes. Beside its well-known functions, antidiuretic hormone has a role in social behavior as it enhances aggression via vasopressin receptor 1A. Oxitocin is affected in the formation of maternal behavior, and in other social interactions, like the pair bounding, as well as in analgesia and pain modulation. The corticotrop-releasing hormone acts as a neurotransmitter, it has a special role in stress-behavior, anxiety, and depression, and it blocks deep sleeping. Among the neurotransmitters and neuropeptids of the hypothalamus, serotonin, norepinephrine, GABA, cholecystokinin, neuropeptide-Y, Agouti-related protein, alpha-MSH and ghrelin have essential importance in the eating disorders. The levels of leptin and galanin determine whether formation of anabolic or catabolic neurotransmitters should take place. In the thermoregulation the central thermoreceptors play role, and suprachiasmatic nucleus is responsible for circadian rhythm, through "timing genes". The diseases of the hypothalamus cause most frequently bulimia or anorexia, hypersomnia, impotency, and attacks of anxiety. The most common expansive process of the hypothalamus is craniopharyngioma. The lack or diminution of vasopressin causes diabetes insipidus, while inappropriate antidiuretic hormone secretion induces Schwartz-Barter syndrome. Fröhlich-, Kleine-Levin- or Prader-Willi syndromes have characteristic neuropsychiatric features. The main psychiatric symptom of hypopituitarism is a combination of dementia and delirium. The most characteristic neurological sign of pituitary adenoma is the visual field defect. Carpal tunnel syndrome, obstructive sleeping apnoe and headache are typical neurological features in somatotrop adenomas.

[Hepatitis C viral infection and depression]. / Hepatitis C vírusfertozés és depresszió.

About 170 million individuals can be found with chronic hepatitis C viral infection all over the world. The occurrence of depression is more frequent among the persons than in the healthy population, this depression can be found in 58 per cent of patients with chronic hepatitis C. On the basis of the literature the authors review the aetiology of depression in liver diseases, examining the neuropathogenic effect of HCV. They demonstrate the scientific results which are evidences of hepatitis C viral infection for the alterations in the central nerve system. The depression is one of the side effects of the alpha-interferon treatment used in the therapy of HCV. The authors demonstrate the biological basis, development, consequences of depression produced by interferon and they give a review of the protocol in the diagnostic procedure of a patient with depression. They summarize the steps of psychiatric drug therapy in chronic liver diseases. That is also important whether the chronic HCV infected patient with depression can be treated with interferon. The loss of interferon treatment can lead to the fatal outcome of liver disease. In order to have the correct decision a collaboration between internist and psychiatric specialist is necessary.

[Some neurologic and psychiatric complications in endocrine disorders: the thyroid gland]. / Néhány endokrin betegség neurológiai és pszichiátriai vonatkozása: a pajzsmirigy.

Thyroid hormones are of primary importance for the perinatal development of the central nervous system, and for normal function of the adult brain. These hormones primarily regulate the transcription of specific target genes. They increase the cortical serotonergic neurotransmission, and play an important role in regulating central noradrenergic and GABA function. Thyroid deficiency during the perinatal period results in mental retardation. Hypothyroidism of the adults causes most frequently dementia and depression. Other less common clinical pictures include myxoedema coma, dysfunction of cerebellum and cranial nerves. Hypothyroidism also increases predisposition of stroke. Peripheral diseases frequently include polyneuropathy, carpal tunnel syndrome, myalgic state, and rarely myokymia. Nearly all the hyperthyroid patients show minor psychiatric signs, and infrequently psychosis, dementia, confusion state, depression, apathetic thyrotoxicosis, thyrotoxic crisis, seizures, pyramidal signs, or chorea occur. The peripheral complications may be indicated by chronic thyrotoxic myopathy, infiltrative ophthalmopathy, myasthenia gravis, periodic hypokalemic paralysis and polyneuropathy. Generalized resistance to thyroid hormone was confirmed in a number of patients with attention deficit-hyperactivity disorder. Significantly elevated antithyroid antibody titers characterize Hashimoto's encephalopathy. This condition is a rare, acute - subacute, serious, life threatening, but steroid-responsive, relapsing-remitting, autoimmune disease.

[Effects of antidepressants on sleep]. / Az antidepresszánsok hatása az alvásra.

Insomnia and depression are widespread diseases causing deterioration of life's quality and increasing morbidity and mortality of cardiovascular diseases. Both of them and certain antidepressants adversely affect physiological structure of sleep, while others restore it. The latter drugs must be preferred in therapy of depression accompanying insomnia, and some of them may be effective in treatment of insomnias without depression. Most antidepressants cause REM-reduction, generally with increased serotonin-function. Selective H1-antagonists readily induce sleep, and also the inhibition of cholinergic neurons in the general arousal networks promotes sleep. Sleep continuity is improved by the rise of synaptic level of serotonin. Among tricyclic antidepressants trimipramine and amitriptyline are the best to improve sleep. However, the former has low antidepressant effect and the latter has many adverse side effects. Selective serotonin reuptake inhibitors, except paroxetine, improve sleep only at the time and to the extent of restoring depression. Paroxetine has beneficial effect on sleep at the beginning of the treatment. Mirtazapine is the first-line sleep promoter among atypical antidepressants, however, its effect on increasing appetite markedly limits its application. Trazodone causes hangover, and mianserin may induce restless legs. Insomnias without depression demand lower dose of antidepressants than depression.

Lateralization as a factor in the prognosis of middle cerebral artery territorial infarct.

The consequences of cerebral infarcts involving the left hemisphere differ from those of the right homologue areas. Data of 337 consecutive, unselected patients with acute ischaemic stroke in the territory of the right or left middle cerebral artery were analysed. Furthermore, lesion locations of 77 stroke patients with early death were compared with those of 315 patients followed for more than 28 days. Without any differences in stroke severity and in the volume of the lesions, the outcome of strokes of the right hemisphere was less favourable, and the case fatality rate was higher than in controls during a 10-year follow-up period. The rate of early death due to cardiogenic cause was relatively higher in the right hemispherical group. The asymmetry of the sympathetic nervous system, and the distinct psychosyndromes following the injury of the two hemispheres may underlie this difference in prognosis.