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.

[Septic encephalopathy--prognostic value of the intensity of consciousness disorder to the outcome of sepsis]. / Septicka encefalopatija--prognosticka vrijednost intenziteta poremaca svijesti za ishod sepse.

Septic encephalopathy (SE) is a common term indicating the development of signs of progressing cerebral dysfunction and is associated with the presence of microorganisms and their toxins in the blood. Aim of this investigation was to analyze the frequency of this complication considering the consciousness disorders in quantitative sense and prognosis of the survival in patients with SE. The investigation comprised patients (n = 54) with positive hemoculture and signs of septic syndrome by the accepted criteria (fever, clinical signs of infection, respiratory frequency, heart rate, plasma lactate, oliguria). Patients with confirmed cerebral injury, hemorrhage or cerebral ischemia were excluded from the study. Lumbar punction and CT-scan of the brain were performed in all patients in order to exclude visible lesions of cerebral parenchyma and eventual presence of cerebral nervous system (CNS) infection as the causes of sepsis. Results of the investigation demonstrated that in 30 (55%) of patients existed mild consciousness disorder at the level of somnolescence, in 18 (33%) consciousness disorder at the level of sopor and in 6 (11%) consciousness disorder at the level of deep coma. Level of consciousness disorder was in positive correlation with the outcome of sepsis syndrome, which was additionally confirmed by the fact that only in the group of patients with deep coma lethal outcome was observed in 3 cases (50% of this subgroup) regardless of intensive antibiotic, metabolically active and symptomatic therapy. It can be concluded that SE syndrome has a favorable prognosis if macroscopic lesion and dissemination of microorganisms in CNS are not present, and simultaneously it represents changes in metabolic-electrolytic state with early presentation of consciousness disorders that represent clinically significant indicator for sepsis syndrome outcome.

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 closed head injury syndrome--frequency and character of brain parenchyma lesions]. / Sindrom zatvorene povrede glave--ucestalost i karakter lezija mozdanog parenhima.

The aim of this investigation was to determine the frequency and character of the brain parenchyma lesions using CT scan and MR in patients with closed head injury, and afterwards to establish the connection of those changes with clinical parameters (neurological deficit and the degree of consciousness disorder), evaluating the sensitivity and specificity of neuroradiological procedures. The investigation comprised 40 patients with closed head injury. Grade of neurological deficit (Canadian Neurological Scale) and the degree of consciousness disorder (Glasgow Coma Scale) were determined in all patients by the same neurologist. The results revealed significantly higher specificity and sensitivity of brain examination using MR in patients with closed head injury, particularly in the detection of small ischemic and contusion lesions. Likewise, the correlation of positive findings using MR was more significant concerning the grade of neurological deficit and the degree of consciousness disorder compared to the brain examination using CT scan.

[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.

Significance of de-novo IgD and IgM synthesis in CSF of patients with relapsing-remitting form of disseminated demyelinating disease of CNS.

Disseminated demyelinating disease of the central nervous system (DDD CNS) is immunologically mediated, with confirmed significant intrathecal immunoglobulin production. According to recently known immunopathogenic occurrences and activation of humoral immune response, we have assumed that the presence of oligoclonal immunoglobulins of M and D classes can be confirmed in cerebrospinal fluid (CSF) of patients with DDD CNS. With the aim of its further determination in CSF of relapsing-remitting DDD CNS patients in either remission and relapse phase, respectively, we have confirmed the presence of oligoclonal IgD and IgM bands, the association of this production and the presence of new demyelinating zones found by MRI of endocranium, as the time elapsed from the last relapse until the obtaining of CSF for further analyses. Method of isoelectric focusing with Western blott procedure was used for the confirmation of oligoclonal IgM and IgD bands presence in CSF. Significant presence of intrathecally synthetized oligoclonal IgM and IgD in patients with DDD CNS in exacerbation phase was presented. Almost in all patients in this phase was found at least one indicator of acute phase (positive MRI finding, presence of oligoclonal IgM or IgD bands). Significant decrease of positive findings of oligoclonal Ig bands in CSF was correlated with the time elapsed from the onset of relapse until the obtaining of CSF for the analysis due to short half-life of those Ig in CSF.

The significance of determination of the fraction of creatinine-phosphokinase in patients with acute ischemic brain disease.

Heart and brain vascular diseases are the leading causes of mortality in the world. Cardiac complications can frequently occur during the development of cerebral ischemia. The aim of this study was to establish the possible changes in fractions of creatinine-phosphokinase as the sensitive laboratory index of parenchymal lesion of brain parenchyma and the presence/absence of risk factors for ischemic brain and heart disease. The study comprised 80 patients with acute ischemic brain disease (AIBD), without the history of previous coronary disease. Blood samples were taken in all patients within the first 48 hours from AIBD onset aiming to determine a total (muscular MM) and heart fraction of creatinine-phosphokinase (MB), and brain parenchyma ischemia was confirmed by CT or MR scan of the head. A detailed history of the risk factors for ischemic brain disease (IBD) and ischemic heart disease was taken from all patients with AIBD, and the profile of glycemia and lipid status were determined, and blood pressure was measured 6 times a day. Independent variables in statistical analysis were: age, degree of severity and the side of neurologic event, size of ischemic lesion and maximal values of systolic and dyastolic pressure. Dependent variables were the values of fractions of creatinine-phosphokinase (CPK). Control group (n = 40) comprised patients with neurologic diseases of non-vascular origin. All parameters as well as their interrelations were statistically analyzed. The results revealed significant correlation of the increased levels of CPK of MM and MB fraction with the size and place of ischemic lesion in the right cerebral hemisphere, which was highly significant for MB fraction in the total group of patients with AIBD, and for MM fraction, only for cases of more severe IBD. Highly significant increased values of those fractions were also observed compared to the control group of patients.

The value of ophthalmoscopy in the diagnosis of arterial hypertension in patients with ischemic brain disease.

Beside dyslipoproteinemia, one of the key risk factors for the onset of brain atherosclerosis, as well as ischemic brain disease (IBD) is arterial hypertension. Significant number of patients is not aware of their hypertension, and a paradoxical blood pressure decrease can occur at the onset of IBD, due to the failure of autoregulation mechanisms. Likewise, valid anamnestic data can not frequently be obtained due to difficulties in communication with patients. Regarding these facts, our hypothesis was that ophthalmoscopy in patients with IBD had the greatest sensitivity in the diagnosis of hypertensive disease, its duration and severity. For that reason, the purpose of this study was to determine the significance of ocular fundus examination in those patients with IBD who were not aware of their hypertension, or the high blood pressure was not registered at the admission. Study comprised 140 IBD patients selected upon the following criteria: ophthalmoscopy was performed by the same ophthalmologist, and IBD was diagnosed according to clinical criteria and by brain computerized tomography. Results of the study demonstrated that 26 (18.6%) patients, although not aware of having hypertensive disease, had grade I hypertonic fundus, 14 (10%) had grade II, and 8 (5.5%) had grade III hypertonic fundus, which indicated the high sensitivity of ophthalmoscopy in the diagnosis of hypertensive disease, as well as its duration and severity. This is particularly important in patients with negative history of hypertension, and also suggests the significance of routine ophthalmoscopy in normotensive patients.

[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.

[Neurologic manifestations after surgical interventions]. / Neuroloske manifestacije nakon hirurskih intervencija.

Administration of general anesthesia is rarely accompanied with newly developed postoperative neurological complications. We analyzed postoperative complications after general anesthesia where an urgent neurologic assistance was necessary. The investigation included 120 patients. The same neurologist performed neurologic examination and electroencephalography, and computerized tomography (CT) was performed if necessary. In 96 (80%) patients focal stimulative or destructive phenomena such as epi-seizures or neurologic deficit were not detected by neurologic examination. In 9 (7.5%) patients were detected consciousness crisis. In 6 patients (5%) were registered right extremities weakness with motor dysphasia, which was withdrawn in first 24 hours. In these cases EEG revealed weak activity in theta frequency, above frontoparietal regions, bilaterally. In 6 (5%) patients was registered neurologic deficit of hemiparesis or semi-severe degree with development of ischemic lesion confirmed by CT. In 6 (5%) patients, CT scan revealed the presence of mild brain edema. Also, positive correlation between duration of anesthesia, age and metabolic disorders, specially diabetes mellitus, was found. We concluded that age, type of surgical intervention and duration of general anesthesia had the greatest influence on the development of neurologic disorders during and after general anesthesia, and the presence of metabolic disorders and previous brain damage increase the risk for the onset of these complications.

[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.

[Multiple sclerosis and epilepsy]. / Multipla skleroza i epilepsija.

Epileptic seizures in the patients with multiple sclerosis (MS) were reported more than 100 years ago. The question of mutual physiopathologic association between MS and epilepsy is even nowadays controversial. The question is if epileptic seizures are the symptoms of MS or are just coincidential, i.e., are those two separate neurological diseases? The development of contemporary immunologic, electrophysiologic and neuroradiological diagnostic procedures enabled the diagnosis of MS to be much more certain, and in that way the differentiation of some symptoms and signs, as well as epileptic seizures in those patients became more reliable. In this report are presented three patients in whom the diagnosis of MS was confirmed by clinical, laboratory, immunological, electrophysiological and neuroradiological diagnostic analyses and procedures, and in whom were simultaneously clinically and/or electrophysiologically (EEG) registered epileptic seizures with specific alterations in EEG that were obviously associated with the development of primary disease--MS.

[Stress ulcer in a patient with a subacute subdural hematoma]. / Stres ulkus kod bolesnika sa subakutnim subduralnim hematomom.

During the onset and development of pathologic events, numerous changes occur in the body as the result of an attempt of dynamic equilibrium maintenance. Results of such sequence of events may lead to organic, as well as psychic impairment of the body that is often referred to as the onset of psychosomatic disease. This paper deals with the disorder that could provide better insight in the possible physiopathologic mechanisms of psychosomatic disease or disorders. In a patient, chronic alcoholic subdural hematoma was diagnosed. Peptic ulcer hemorrhage occurred after surgical removal of the hematoma. Possible physiopathologic mechanisms in the origin of this disorder have been described.