Long-term outcome in Serbian patients with Wilson disease.

BACKGROUND AND PURPOSE: To investigate survival rates, prognostic factors, and causes of death in Wilson disease (WD). METHODS: In the years 1980-2007, a cohort of 142 patients with WD was prospectively registered (54 presented with neurologic symptoms, 49 with hepatic symptoms, 33 had mixed form, and data were missing for six patients). The duration of follow-up for patients alive was 11.1 +/- 8.8 years. RESULTS: After initiation of treatment (d-penicillamine and zinc salts), 79% of patients had a stable or improved course of disease. Despite early diagnosis and appropriate therapy, 15 patients still had a relentlessly progressive course. Thirty patients died. The cumulative probability of survival in a 15-year period for the whole group was 76.7 +/- 4.9%. Better prognosis of WD was associated with male sex, younger age at onset, neurologic form of the disease, and treatment continuity. Causes of death were predominantly related to hepatic failure (16 patients), but also suicide (four patients) and cancer (three patients). CONCLUSION: Despite the relatively early diagnosis and treatment of our patients with WD, mortality was still considerably high.

The increase of neuron-specific enolase in cerebrospinal fluid and plasma as a marker of neuronal damage in patients with acute brain infarction.

Our goal was to determine the neuron-specific enolase (NSE) concentration in cerebrospinal fluid (CSF) and plasma in patients with the acute brain infarction (BI) and analyze the correlation between the measured NSE concentration and infarct volume and the degree of neurological and functional deficit. The study included 55 patients aged 56-68 with BI in the acute phase. The control group consisted of 16 patients subjected to diagnostic radiculography. The results showed a significant increase of NSE concentration within the first seven days in patients compared to the controls (2.838 +/- 0.504 ng/ml CSF and 4.479 +/- 0.893 ng/ml plasma). A significant correlation was found between NSE concentration and infarction volume and the degree of neurological and functional deficit both in the CSF (r = 0.828, r = 0.735, r = 0.796; p < 0.001) and in plasma (r = 0.810, r = 0.681, r = 0.783; p < 0.001). The results suggest that an early determination of this marker in CSF and plasma in patients with BI could be a valuable diagnostic factor.

[Comparative study of the analgesic effect of Dikalm and Saridon in headaches of various causes]. / Uporedno ispitivanje analgetskog efekta Dikalma i Saridona u slucaju glavobolja razlicitog porekla.

Headache, as a syndrome, represents large health and wider socio-economic problem in every community for its massive occurrence and frequent absence of therapeutic response to the administered analgesics. That is why the finding, and later production of the drug that would satisfy the criteria of analgesic, efficacious in the treatment of headache, without the entering in etiology of syndrome are presented as the imperative. In connection with that was set the aim of the investigation: to investigate comparative analgesic efficacity of new preparation--Dikalm compared to analgesic that was for a long time present in our pharmaceutic market--Saridon tablets in the patients with different neurologic diseases, where headache represents the leading symptom of their difficulties. The investigation included 30 patients--10 patients were cross-examined with the use of both preparations in the treatment of headache episodes that appeared in separate time interval, and 20 patients received one another preparation. The headache intensity, residual headache, adverse effects and the need for repeating were graded by original standardized scales. The results of investigation revealed significantly better analgesic effect of therapeutic combination contained in Dikalm preparation, as for persistent, residual headache, as for the need of repeating the analgesics administration, what was specially pronounced in the group that cross-received both preparations, or in the whole group compared to the therapeutic combination contained in Saridon tablets. It was concluded that Dikalm represented the drug with efficacious analgesic and with minimal adverse effects.

[Analgesic efficacy of Famalgin and Imigran in patients with acute migraine attacks]. / Ispitivanje analgetske efikasnosti Famalgin-a i Imigran-a kod bolesnika sa akutnim migrenskim atacima.

Migraine is a syndrome clinically manifested in attacks which dominant symptom is unilateral, rarely generalized, recurrent headache that can last for hours, and occasionally, days. According to different sources, it is considered that about 10-15% of world population suffers from some type of this syndrome. Migraine is most frequently clinically revealed in the age of 30-40, therefore in the most productive period with significant share in treatment costs and a great influence to the working ability of those patients. The aim of this trial was to determine analgesic efficacy of Imigran (sumatriptan) and Famalgin in the treatment of acute attacks of migraine headache. Trial results revealed significant analgesic efficacy of both preparations without significant differences in analgesic effect, with significantly better tolerability of Famalgin. It was concluded that both preparations were efficacious drugs for the treatment of headache as the most prominent clinical symptom of migraine, with significantly rarer and less pronounced adverse effects of Famalgin.

The effects of local application of 1% dopamine on intraocular pressure and pupillary diameter.

This paper deals with the experimental results of the effect of 1% dopamine on intraocular pressure, pupillary diameter and hemodynamic parameters after its local application in the rabbit eye. Our results show that locally applied dopamine caused an initial increase of intraocular pressure (IOP) (1 h), followed by its decrease that was the most pronounced 3 hours later. Mydriasis was an immediate effect of dopamine, which persisted until the end of the second hour. There were no changes in blood pressure and heart rate. Although the exact mechanism of dopamine effect on IOP is not known yet, our results point out that this is mainly due to the decrease fo aqueous humor formation.

[Effect of aging on visual evoked potentials]. / Uticaj starenja na vidne evocirane potencijale.

Experimental and clinical studies, aiming to establish the influence of aging on latence, amplitude and types of waves of visual evoked potentials (VEP) are numerous. It was concluded that P-100 latence prolonged with aging, particularly after the age of 55, while P-100 amplitude had been gradually decreased during the life. During the aging, senile changes in the eye and optic nerve (for example, senile miosis, degenerative retinal changes, geniculostraital defect) can be reflected to the changes in VEP (P-100). Aim of our study was to establish if the aging influences the alteration in latence and wave amplitude in VEP, as well as to standardize normal values of VEP in different ages. VEP was registered in 135 subjects classified into 3 groups. Group I comprised 49 subjects, aged 17-30 (average age 20.92 years), group II comprised 34 subjects aged 31-54 years (average 42.55 years). Group III--over 55 years (average age 69 years) comprised 52 subjects. There were 55 females and 80 males. Results have shown that the mean value of amplitude for both eyes in the first two groups of younger subjects was 9.03 microV and 8.91 microV, respectively, while in the group of older subjects, it was slightly decreased--8.54 microV. P-100 latence prolonged insignificantly until the age of 55, and afterwards in every 5 years it increased for 1.5 ms. Amplitude was insignificantly lower latence in VEP was insignificantly prolonged until the age of 55, and afterwards, the increase was significant. Amplitude was decreased insignificantly, gradually during the life.

Brain oxidative stress in the syndrome of mutual aggravation on the model of combined injury in Mongolian gerbils.

General reaction of an organism (survival, body temperature, hematocrit, glycemia) was followed in Mongolian gerbils subjected to isolated head injury (brain ischemia--LD5), to peripheral injury (ischemia of both hind limbs--LD20), and to combined injury (head injury + peripheral injury). In the early period (1 hour) after the injury, parameters of oxidative stress were followed in the brain cortex (superoxide anion, index of lipid peroxidation, activity of superoxide dismutase and glutathione reductase). Obtained results indicate that the combined peripheral and central injury of low lethality leads to the worsening of general response of the organism with high lethality of experimental animals (LD80). Likewise, the increased cortical production of superoxide anion and index of lipid peroxidation, as well as the disturbances of antioxidative enzymes activity suggest on an important role of brain oxidative stress in the development of the syndrome of mutual aggravation in animals subjected to combined injury.

The significance of hemispheric localization of ischemic brain lesion for the early prognosis of ischemic brain disease.

The possibility of early prediction of ischemic brain disease (IBD) is extremely significant for the creation of the individually designed treatment program. The aim of this study was to determine the significance of hemispheric localization of ischemic brain lesion as possible factor for the early prediction of IBD outcome. The study included 170 patients with IBD, whose score of neurologic and functional impairment was determined after admission by using the standard scales. The values of hemorrheological parameters-erythrocyte sedimentation rate (ESR), fibrinogen and alpha 2 globulin were also determined, so as the extensity of ischemic lesion by CT and MR brain examinations. After the treatment, the score of neurologic and functional impairment was also determined and the degree of ischemic disturbance was estimated-transitory ischemic attack (TIA), reversible ischemic attack (RIA) and cerebral infarction. The lower scores were noticed for neurologic and functional impairment, meaning the more severe degree of ischemic disorder with ischemic lesion localization in right cerebral hemisphere (RCH), in acute stage and at the end of treatment. The higher values of ESR, slightly less of fibrinogen and alpha 2 globulin were revealed in the case of ischemic lesion localization in RCH, so as the higher frequency of RCH lesions in percentages connected with the more severe ischemic disorders. It was concluded that the ischemic lesion localization in RCH might be the predictor of poorer IBD outcome.

Increased titer of anticardiolipin antibodies represents the risk for the development of ischemic brain disease in persons below 50.

The aim of this paper was to investigate the frequency of increased ACLA titer in patients with ischemic brain disease (IBD) and to define their clinical profile. The group consisted of 162 IBD patients of both sexes, aged 39-81 years, with 50 healthy volunteers and 23 patients with other neurological diseases as control. Increased ACLA titer (above 0.9 GPL U/l IgG and 0.5 MPL U/l IgM) was registered in 17.9% IBD patients, and more frequently in patients with transitory ischemic attacks (TIA)-32.6%; slightly increased titer predominated (0.9-20 GPL U/l IgG and 0.5-15 MPL U/l IgM) in 69% IBD patients, while moderately increased (20-80 GPL U/l and 15-50 MPL U/l IgM) was present in 21% IBD patients, while highly increased titer (above 80 GPL U/l IgG and above 50 MPL U/l IgM) was present in 10.3%; IgG class was most frequently increased (9.2%), than IgM-5%, while increase of both classes was present in 3.7%. All patients with increased ACLA titer were below 50 years of age, had history of previous IBD attacks, more often TIA, irregularity of at least one coagulation test and fewer risk factors for IBD. Hence, increased ACLA titer was present in IBD patients of both sexes, below 50 years of age with previous history of IBD attacks and fewer atherosclerosis risk factors.

[Significance of proteinuria in patients with acute ischemic brain disease]. / Znacaj proteinurije kod bolesnika sa akutnom ishemijskom bolescu mozga.

Brain vascular diseases are ranked the third as the cause of morbidity and mortality in majority of the countries of the world. In about 80% of the cases of vascular brain diseases, it is ischemic brain disease (IBD). Atherosclerosis of main cerebral arteries is most frequently responsible for the occurrence and development of IBD. In recent years it was reported for the first time of the association of atherosclerosis and/or its complications and proteinuria. Assuming that there exists the significant association between the degree of proteinuria and clinical parameters of IBD, the aim of this study was to investigate the frequency and patterns of the association of proteinuria and clinical IBD parameters. The study was performed in 180 patients with IBD of atherothrombotic origin and 60 patients with the diseases of non-vascular origin, as the control group. In all patients quantitative determination of proteinuria was performed, and in the patients with IBD was determined the degree of IBD and afterwards the degree of functional and neurologic impairment prior to and at the end of treatment in acute phase using the standardized scales. The results of the study revealed the existence of significant frequency of proteinuria in the patients with IBD, as well as the significant association between the degree of proteinuria and severity of IBD. It was concluded that proteinuria in patients with IBD was probably associated with the atherogenic processes and physiopathologic processes of IBD, respectively, which could have predictive value for the outcome of the disease in the early stage.

[Therapeutic value of antioxidants and calcium channel blockers in patients in the acute phase of closed head injuries]. / Terapijska vrijednost antioksidanasa i blokatora kalcijumski kanala kod bolesnika sa zatvorenom povredom glave u akutnoj fazi.

Knowing that uncontrolled calcium signalization with excessive production of reactive oxidative matters is present in case of neurotrauma, aim of the investigation was to establish therapeutic value of combined administration of antioxidants (AO) and calcium channel blockers (CCB) in patients with closed head injury (CHI). Investigation comprised 120 patients with CHI who received AO (vitamins C and E) parenterally during 10 days and CCB (nimodipine), and control group was comprised of 60 patients with CHI who did not receive these medicinals in therapeutic program. We have established the influence of the therapy on neurologic and functional deficiency and consciousness disorder, respectively. Results of the investigation confirmed better recovery of all three observed parameters (degree of neurologic deficiency, degree of functional deficiency and consciousness disorder) in a group of patients receiving AO and CCB, which was statistically significant. It can be concluded that the administration of AO and CCB in patients with CHI in the acute phase should be included into therapeutic program of this significant clinical syndrome.

[Anatomic and physiologic characteristics of the peritoneal cavity with reference to peritoneal dialysis]. / Anatomske i fizioloske osobine peritoneumske supljine od znacaja za peritoneumsku dijalizu.

Most common complications of peritoneal dialysis are those related to anatomic defect of the abdominal wall and peritoneum. The aim of this investigation was to examine the frequency of congenital and acquired wall defects in patients on CAPD treatment causing complications. Fifty patients, 32 women and 18 men, on CAPD treatment for more than two years, were investigated. Most common was a defect in the anterior-lateral abdominal wall predisposing to hernias in 14% of patients. Umbilical and pericatheteral hernias were more common than other, with a mean time of 21 months for the appearance. Persistence of vaginal process of peritoneum related to scrotal oedema was documented in 4% of patients. Communication of peritoneal cavity with the abdominal ostium of tuba uterina was found not to be an important factor for peritonitis.

[Convulsion-conversion epilepsy--a problem in differential diagnosis]. / Konvulzijsko-konverzijska epilepsija--diferencijalnodijagnosticki problem.

Epilepsy is chronic, multietiologic disease of the cerebrum, with different clinical features and with frequent occurrence of emotional and psychic disorders. In this report, we presented the case of female patient, 16 years old, examined in our Clinic twice. The diagnosis of epilepsy was established on the basis of the following examinations (EEG, Holter EEG, MR of the head) and Carbamazepine was included in the therapy. Afterwards, in the patient, instead of grand mal seizures, occurred atypical nonconvulsive prolonged seizures, without postictal phenomena, and after the repeated observation, psychological confrontation and according to the bizarreness of certain seizures the case of conversional-convulsive epilepsy was confirmed, and for that reason we decided to publish this report.

[Carotid-cavernous fistula with spontaneous remission]. / Karotidno-kavernozna fistula sa spontanom sanacijom.

Carotid-cavernous fistulas (CCF) represent the complication of traumatic injuries mostly of bone structures of skull base and face, and rarely of soft neck tissues with the fast development of the shunt and imperiled hemodynamics that in a short time endangers the patient for the increase of intracranial mass. The therapy of this clinical entity significantly changed in the last few years. In this report, we present the case of spontaneous CCF healing with the complete restitution of neurological deficit and CCF healing in control angiographies.

[Neurologic disorders in a patient with autoimmune hemolytic anemia]. / Neuroloski poremecaji kod bolesnika sa autimunskom hemolitickom anemijom.

Completely different entities might be with the same possibility in the baseline of interweaving of symptoms and signs of nervous system damage. One of them, the deficiency of vitamin B12 very frequently causes megaloblastic anemia and funicular myelosis. In the case of our patient, after the clinical picture of hemolytic anemia was revealed, by slow-progressive course was developed neurologic deficiency that, according to its features, could have the deficiency of cobalamin and folic acid in its etiologic background. On the basis of disease course, clinical finding, numerous clinical investigations so as the reaction to applied therapy it was assumed that the patient had besides confirmed autoimmune hemolytic anemia the pernicious anemia as the associated cause of anemic syndrome and the basic reason of the development of neurologic deficiency. Described is the frequent associated occurrence of pernicious anemia and antiglobulin positive hemolytic anemia, so as the significant association of pernicious anemia with the deficiency of immunoglobulins that was otherwise observed in our patient as the permanent IgA deficiency.

Clinical predictors of cardiac complications in patients with acute ischemic brain disease.

Heart and brain vascular diseases present leading causes of death in civilized world. During development of brain ischemia cardiac complications are possible. The aim of this study was to determine the existence of cardiac complications' clinical predictors by assessing certain electrocardiographic changes in patients with acute ischemic brain disease (AIBD). Forty patients with AIBD, without previous coronary disease history were included in the study. All patients underwent 24 hour Holter monitoring during first 48 hours after the onset of AIBD which was diagnosed by computerized brain tomography. ECG-s were analyzed by computer and interpreted by the same cardiologist. Independent variables in statistical analyses were: age, AIBD, cardiological therapy atherosclerosis risk factors, heart disease history, degree of severity and lateralization of neurological incident and maximal arterial blood pressure values. Dependent variables were: presence/absence of ST depression and presence/absence of ventricular arrhythmias (VA). All parameters as well as their interreaction, were statistically analyzed. Results point that age and side of neurological incident present independent important predictive factors for appearance of ST depression, as well as simultaneous heart ischemia, while the same parameters have border value as predictive factors for VA.

[Progressive multifocal leukoencephalopathy]. / Progresivna multifokusna leukoencefalopatija.

Progressive multifocal leukoencephalopathy (PML) is rare and very severe disease, classified into the group of subacute and viral infections of central nervous system (CNS), and can simulate clinical pictures of numerous degenerative diseases of nervous system. PML was firstly described in 1958, and pathologic-morphologic substrate was explained in papers of Astron et al. Many years later, definitive diagnosis of PML was histopathologic, on the autopsy material. The fact that it is very rare and severe disease, very rarely diagnosed in clinical conditions, is the reason of our decision to present this case.

[Alpha coma--a prognostic sign?]. / Alfa-koma--prognosticki snacaj?

We present a patient who has developed cardiac arrest after penetrating cardiac wound and consequent coma, with EEG characteristics of alpha coma. At the same time, auditory evoked potentials-brainstem (AEPB), subcortical and cortical were not within physiological range. During the sixth day of coma, alfa rhythm was substituted with theta and delta frequency, followed by the decreased amplitude and prolonged latency of AEPB and complete absence of cortical and subcortical responses. Lethal outcome occurred in the fifth week of coma with neurophysiological characteristics of complete brain dysfunction. Alpha coma, with EEG presentation that only resemble the normal neurophysiological cortical activity, is rather rare neurophysiological finding present mostly in cardiac arrest, metabolic disturbances and intoxication. It is probably caused by pathological pacers of alfa rhythm, so clinical presentation of alfa coma, specially in a case of cardiac arrest, does not predict a favourable outcome.

[The Fahr syndrome]. / Farov sindrom.

Fahr's syndrome is a rare clinical entity consisting of certain metabolic, biochemical, neuroradiologic and neuropsychologic phenomena in which extrapyramidal phenomenology clinically dominates. In this report, primarily from educational reasons, we have presented a female patient, who was before admittance to our clinic examined in one Belgrade hospital for headache, stiffness of trunk and extremities and the diagnosis was migraine with depressive reactions. However, as the discomforts were persistent, she was admitted to our clinic and after the investigation, especially for the presence of extrapyramidal clinical phenomenology with dominantly pronounced increase of tonus with the presence of amorphous calcifications in basal ganglia on both sides it was concluded that she was suffering from Fahr's syndrome.

[Diagnostic and prognostic significance of long latency reflexes, somatosensory evoked potentials and the blink reflex in cerebral ischemia]. / Dijagnosticki i prognosticki znacaj refleksa dugih latenci, somatosenzornih evociranih potencijala i refleksa treptanja kod ishemijske bolesti mozga.

In order to determine diagnostic and prognostic value of long latency reflexes, blink reflex and somatosensory evoked potentials in patients with ischemic brain disease (IBD), examinations were done in 32 patients of both sexes with IBD, average age 44-76 years. First examinations were performed within first week of the onset of IBD and in majority of patients repeated after 3 and 6 months. Changes of electrophysiological characteristics compared with the degree of IBD, clinical presentation, localization, extent of infarction zone (measured by CT) and functional recovery where analyzed. Electrophysiological changes were predominantly associated with amplitude of physiological response and were in correlation with the degree of IBD, localization and the extent of infarction zone. Latencies were prolonged only in case of subcortical ischemic lesions. Correlation between functional recovery and electrophysiological changes was present only within the structures responsible for certain components of electrophysiological responses and localization of ischemic lesion. In conclusion, electrophysiological examinations are of high diagnostic and predictive value in IBD.