EAN guideline on palliative care of people with severe, progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. METHODS: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients-Intervention-Comparator-Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20 m without resting (Expanded Disability Status Scale score > 6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. RESULTS: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient's wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. CONCLUSIONS: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs.

Patient and caregiver involvement in the formulation of guideline questions: findings from the European Academy of Neurology guideline on palliative care of people with severe multiple sclerosis.

BACKGROUND AND PURPOSE: Patient and public involvement in clinical practice guideline development is recommended to increase guideline trustworthiness and relevance. The aim was to engage multiple sclerosis (MS) patients and caregivers in the definition of the key questions to be answered in the European Academy of Neurology guideline on palliative care of people with severe MS. METHODS: A mixed methods approach was used: an international online survey launched by the national MS societies of eight countries, after pilot testing/debriefing on 20 MS patients and 18 caregivers, focus group meetings of Italian and German MS patients and caregivers. RESULTS: Of 1199 participants, 951 (79%) completed the whole online survey and 934 from seven countries were analysed: 751 (80%) were MS patients (74% women, mean age 46.1) and 183 (20%) were caregivers (36% spouses/partners, 72% women, mean age 47.4). Participants agreed/strongly agreed on inclusion of the nine pre-specified topics (from 89% for 'advance care planning' to 98% for 'multidisciplinary rehabilitation'), and <5% replied 'I prefer not to answer' to any topic. There were 569 free comments: 182 (32%) on the pre-specified topics, 227 (40%) on additional topics (16 guideline-pertinent) and 160 (28%) on outcomes. Five focus group meetings (three of MS patients, two of caregivers, and overall 35 participants) corroborated the survey findings. In addition, they allowed an explanation of the guideline production process and the exploration of patient-important outcomes and of taxing issues. CONCLUSIONS: Multiple sclerosis patient and caregiver involvement was resource and time intensive, but rewarding. It was the key for the formulation of the 10 guideline questions and for the identification of patient-important outcomes.

Identification of mutations in the PARK2 gene in Serbian patients with Parkinson's disease.

Mutations in the PARK2 (PRKN) gene are the most common cause of autosomal-recessive (AR) juvenile parkinsonism and young-onset Parkinson's disease (YOPD). >100 different variants have been reported, including point mutations, small indels and single or multiple exon copy number variations. Mutation screening of PARK2 was performed in 225 Serbian PD patients (143 males and 82 females) with disease onset before 50 years and/or positive family history with apparent AR inheritance. All coding regions and their flanking intronic sequences were amplified and directly sequenced. Whole exon multiplications or deletions were detected using Multiple Ligation Probe Amplification (MLPA) method. We identified 12 PD patients with PARK2 mutations (5.3%). Five patients (2.2%) had biallelic mutations and seven (3.1%) were single mutation carriers. Patients with compound heterozygous mutations had earlier onset of the disease compared to non-carriers (p = 0.005) or heterozygotes (p = 0.001). Other clinical features in mutation carriers were not different compared to non-carriers. In our cohort, sequence and dosage variants were equally represented in patients, inducing their first symptoms mainly before the age of 30. For efficient genetic testing strategy, patients with early, especially juvenile onset of PD were strong candidates for both dosage and sequence variants screening of PARK2 gene.

Transcranial sonography in dopa-responsive dystonia.

BACKGROUND AND PURPOSE: Mutations in the GCH1 gene, encoding GTP cyclohydrolase 1, the enzyme critically important for dopamine production in nigrostriatal neurons, are the most common cause of dopa-responsive dystonia (DRD), characterized predominantly by limb dystonia, although parkinsonian features may also be present. It has been suggested that DRD is a neurochemical rather than neurodegenerative disorder. METHODS: Transcranial brain sonography, which might be a risk marker for nigral injury, was obtained from 141 subjects divided into four groups: (i) 11 patients with genetically confirmed DRD; (ii) 55 consecutive patients with Parkinson's disease (PD); (iii) 30 patients diagnosed as isolated adult-onset focal dystonia; and (iv) 45 healthy controls (HCs). RESULTS: Substantia nigra hyperechogenicity was present in 63.6% of patients with DRD, which was significantly different in comparison to patients with dystonia (20%) and HCs (6.7%), but not in comparison to the PD group (87.3%). Also, values of the maximal areas of substantia nigra hyperechogenicity in patients with DRD were higher in comparison to HCs, but significantly lower than among the PD group. CONCLUSIONS: We suggested that the observed transcranial brain sonography features in patients with DRD might primarily be risk markers for particular clinical features (parkinsonism, dystonia) occurring in the specific genetic context (i.e. GCH1 mutations), or might reflect compensated neurodegenerative processes triggered by the long-lasting dopamine deficiency due to the profound delay in levodopa treatment in our patients with DRD.

Acute and Late Genitourinary Toxicity after 72 Gy of Conventionally Fractionated Conformal Radiotherapy for Localised Prostate Cancer: Impact of Individual and Clinical Parameters.

AIM: Our aim was to estimate the incidence of acute and late genitourinary toxicity in patients treated with three-dimensional conformal radiotherapy (3DCRT) for localised prostate cancer and to estimate the possible influence of individual and clinical characteristics. MATERIALS AND METHODS: Between September 2009 and September 2013, 225 patients with localised prostate cancer were treated with 3DCRT. Ninety-four patients with an estimated risk of lymph node involvement ≤15%, according to the Roach formula, were evaluated in this study. All patients received a total dose of 72 Gy in 36 fractions. Acute and late genitourinary toxicity were graded according to the European Organization for Research and Treatment of Cancer radiation morbidity scoring scale. Characteristics such as age, smoking status, previous abdominal or pelvic surgery (PAPS), diabetes mellitus and the use of diuretics were analysed as possible predictive factors of toxicity. The median follow-up was 27 months. RESULTS: Grade ≥2 acute toxicity during 3DCRT developed in 25 of 94 patients (26.5%). Predictive factors of acute genitourinary toxicity grade ≥2 in the multivariate logistic regression analysis (MVA) were current smoking status (P = 0.003), PAPS (P = 0.012) and the use of diuretics (P = 0.017). The 2 and 3 year cumulative risk of late genitourinary toxicity grade ≥1 was 25.3% and 30.2%, respectively. In the MVA, acute genitourinary toxicity was significantly associated with late genitourinary toxicity (P = 0.024). CONCLUSION: Current smoking status, PAPS and the use of diuretics have a significant effect on the occurrence of acute genitourinary toxicity grade ≥2. The occurrence of any grade of acute genitourinary toxicity has a significant influence on the development of any grade of late genitourinary toxicity.

Extrathymic malignancies in a defined cohort of patients with myasthenia gravis.

INTRODUCTION: Myasthenia gravis (MG) may be associated with extrathymic malignancies, especially in patients with thymoma. AIM: To determine the frequency and type of extrathymic malignancies in MG patients from the Belgrade area, and to identify potential risk factors associated with tumors. PATIENTS AND METHOD: The study comprised 390 patients with MG. Different sociodemographic and clinical variables potentially associated with extrathymic neoplasms were analyzed. RESULTS: Extrathymic malignancies were present in 42 (10.8%) MG patients - 22 (52.4%) males and 20 (47.6%) females. The most frequently detected were breast (40%) and lung (40%) neoplasms. The tumors appeared with similar frequency before (45.2%) and after the onset of MG (42.9%). Significant predictors for the development of extrathymic malignancies were current age (p = 0.001) and immunoglobulin (IVIg) therapy (p = 0.021). On the other hand, current age (p=0.001), longer MG duration (p = 0.001) and generalized form of MG (p = 0.002) were significant predictors of malignancy occurring after the MG onset. CONCLUSION: Our study revealed that older MG patients, as well as those with longer duration of the disease, and those who received IVIg therapy had a higher oncogenic risk for the development of extrathymic malignancies.

Epidemiological study of adult-onset myasthenia gravis in the area of Belgrade (Serbia) in the period 1979-2008.

BACKGROUND: The aim of this study was to analyze the prevalence and incidence of adult-onset myasthenia gravis (MG) in the Belgrade population from 1979 to 2008. METHODS: Data on the number of MG patients and their basic demographic and clinical characteristics were collected from hospital records (1979-1992) and the Belgrade MG Registry (1993-2008). Incidence and prevalence were standardized by the direct method (using the world standard population). A time-trend analysis of MG incidence was performed using a linear regression model. RESULTS: During the study period 562 cases (316 women, 246 men) were registered. On December 31st, 2008, the standardized prevalence (according to the world standard population) was 188.3/1,000,000 (women: 237.8/1,000,000; men: 139.4/1,000,000). The average annual standardized incidence rate was 13.3/1,000,000 (women: 14.1/1,000,000; men: 12.2/1,000,000). The incidence rates tended to increase significantly in both sexes during the study period (y = 3.299 + 14.363x, p = 0.002). Age-specific incidence rates for women demonstrated a bimodal pattern, with the first peak in the 20- to 29-year age group and the second one in the ≥70-year group. For both genders, an increase in age-specific incidence rates was registered for all age groups, although this was significant (p = 0.001) only for an MG onset of ≥60 years of age. CONCLUSIONS: The study confirms an increase in the incidence of MG in the area of Belgrade during the study period, especially for those with MG onset after 60 years of age.

Long-term adherence to interferon-beta treatment in a cohort of RRMS patients in Belgrade, Serbia.

OBJECTIVE: Long-term adherence to interferon-beta (IFNß) treatment in patients with multiple sclerosis (MS) varies considerably in daily clinical practice. The aim of the present study was to assess the frequency and reasons for stopping the INFß treatment in our relapsing-remitting (RR) MS patients' cohort. PATIENTS AND METHOD: All patients with RRMS initiating treatment with IFNß at the Clinic of neurology, CCS, in Belgrade, from January 2004 to June 2009, were included in the study. Treatment was initiated in RRMS patients with at least two relapses in the previous two years, and EDSS score at entry ≤3.5. During the follow-up, patients underwent regular detailed clinical evaluation performed by MS specialists. RESULTS: The study comprised a total of 290 RRMS patients. During the 6-year follow up period (mean 3.5±2.1 years), 18% of patients stopped the treatment. The main reason for treatment discontinuation was lack of efficacy (54%); 21% of patients stopped therapy because of pregnancy and only 17% because of AE. CONCLUSION: The frequency of treatment discontinuation in our study pointed to the low permanent termination rate reflecting good adherence to IFNß in our RRMS patients. Our results support the notion that long-term adherence to IFNß treatment might be significantly influenced by optimizing the benefits to be achieved from therapy, adequate patient selection and easy accessibility of MS health professionals.

A questionnaire for multinational case-control studies of environmental risk factors in multiple sclerosis (EnvIMS-Q).

OBJECTIVES: The increasing incidence of multiple sclerosis (MS) worldwide, especially in women, points to the crucial role of environmental and lifestyle risk factors in determining the disease occurrence. An international multicentre case-control study of Environmental Risk Factors In Multiple Sclerosis (EnvIMS) has been launched in Norway, Sweden, Italy, Serbia and Canada, aimed to examine MS environmental risk factors in a large study population and disclose reciprocal interactions. To ensure equivalent methodology in detecting age-related past exposures in individuals with and without MS across the study sites, a new questionnaire (EnvIMS-Q) is presented. MATERIALS AND METHODS: EnvIMS-Q builds on previously developed guidelines for epidemiological studies in MS and is a 6-page self-administered postal questionnaire. Participants are de-identified through the use of a numerical code. Its content is identical for cases and controls including 'core' and population-specific questions as proxies for vitamin D exposure (sun exposure, dietary habits and supplementation), childhood infections (including infectious mononucleosis) and cigarette smoking. Information on possible confounders or effect modifiers is also obtained. EnvIMS-Q was initially drafted in English and subsequently translated into Italian, Serbian, Norwegian, Swedish and French-Canadian. EnvIMS-Q has been tested for acceptability, feasibility and reliability. RESULTS AND CONCLUSIONS: EnvIMS-Q has shown cross-cultural feasibility, acceptability and reliability in both patients with MS and healthy subjects from all sites. EnvIMS-Q is an efficient tool to ensure proper assessment of age-specific exposure to environmental factors in large multinational population-based case-control studies of MS risk factors.

Prevalence of multiple sclerosis in the Serbian district Sumadija.

BACKGROUND: The aim of this study was to estimate the prevalence of multiple sclerosis (MS) in the district of Sumadija (central part of Serbia). METHODS: All persons suffering from MS, with permanent residence in the region, were recruited. Prevalence was calculated on December 31, 2006, according to a standard procedure. RESULTS: On December 31, 2006, one hundred ninety-four patients (72 males and 122 females) were found to have MS. We found a crude MS prevalence of 64.9/100,000 (49.3/100,000 for males and 79.9/ 100,000 for females). The highest prevalence rates were registered in the age group of 30-39 years for females and 40-49 years for males, although the age-specific rates were higher in females in all age groups. The mean age at onset was 34.2 ± 9.3 years. The average duration of MS was 8.9 ± 6.2 years. The median EDSS score was 3.9 ± 2.0. The course of MS was relapsing-remitting in 63.9% of patients, secondary progressive in 32.5%, and primary progressive in 3.6%. At MS onset, motor symptoms were present in 70.1% of patients, sensory in 40.7%, cerebellar in 21.1%, brainstem in 15.5%, visual in 22.2%, and bowel/bladder disturbances in 22.2%. CONCLUSIONS: Our results demonstrate that the MS prevalence registered in the Serbian district Sumadija is similar to that of other surrounding areas in Southeastern Europe.

Increased total homocysteine level is associated with clinical status and severity of white matter changes in symptomatic patients with subcortical small vessel disease.

OBJECTIVE: Elevated plasma total homocysteine (tHcy) is an independent risk factor for ischemic stroke and has been linked to cerebral small vessel disease (SVD), in particular. Controversy persists as to whether increased tHcy is associated with functional status and cognitive decline in these patients. METHODS: Plasma tHcy, MTHFR polymorphism, vascular risk factors, functional and cognitive status and severity of lesions on MRI, assessed with the Age-Related White Matter Changes (ARWMC) visual grading scale, were analyzed in 95 patients with SVD and 41 healthy control subjects. RESULTS: Plasma tHcy levels were higher in patients with SVD (14.4±5.0 µmol/L) compared to healthy SVD-free controls (8.9±3.9 µmol/L). In SVD patients, tHcy levels strongly correlated with cognitive status (age-adjusted risk 5.8, 95% CI 1.3-25.3, p=0.015), functional status (age-adjusted risk 3.2, 95% CI 1.2-8.8, p=0.022) and severity of MRI lesions (age-adjusted risk 1.2, 95% CI 1.1-1.4; p=0.004). Only total ARWMC score was independently associated with increased tHcy levels (OR 1.2, 95%CI 1.1-1.4, p=0.004). Independent predictors of WMC occurrence were tHcy levels (OR 1.2, 95%CI 1.1-1.3, p=0.003) and mRS score (OR 2.2, 95%CI 1.2-4.1, p=0.017). CONCLUSIONS: In patients with cerebral SVD there is a positive association of increased plasma tHcy levels with clinical status and severity of WMC.

Outcome of childhood brain tumors in Serbia.

PURPOSE: To present the results of treatment for childhood brain tumors in Serbia. METHODS: The medical records of patients with brain tumors diagnosed and operated at the Institute of Neurosurgery, Clinical Center of Serbia and treated with postoperative radiotherapy and chemotherapy at the Institute of Oncology and Radiology of Serbia, Belgrade, between January 1995 and December 2004, were reviewed. Of the 247 patients who were identified, 212 formed the basis of this study. Overall survival (OS) was determined by the Kaplan-Maier method, using log-rank test for comparisons. RESULTS: With a mean follow up of 46.9-33.6 months (range 7-120), the 5-and 8-year OS rates were 70.0% and 61.5%, respectively. At the time of evaluation 119 (60.1%) patients had no evidence of disease. Among 79 patients who failed therapy, most of them (n=61; 77.2%) had local failure only. According to histologic tumor type most of them (n=27; 34.2%) were in the group of malignant medulloblastoma. Girls had better survival than boys, but without statistical significance (p=0.185). Also, no significant difference in survival in relation to age was seen (p=0.291). Patients with supratentorial tumors had significantly better survival than those with infratentorial localizations (p=0.036). Patients with low grade astrocytomas had significantly better survival than malignant gliomas, ependymomas and primitive neuroectodermal tumors (PNETs) (p=0.0001). CONCLUSION: OS rates were concordant with the results of other modern series. Although the survival rates were encouraging, there is still significant room for improvement in the management of childhood brain tumors.

Epidemiology of Charcot-Marie-Tooth disease in the population of Belgrade, Serbia.

BACKGROUND: The aim of this study was to determine prevalence and 15-year survival in Charcot-Marie-Tooth disease (CMT). METHODS: The study covers the period from 1 January 1988 to 31 December 2007 in the territory of Belgrade. Data on a number of CMT-affected persons and their basic demographic characteristics as well as data on the disease were collected from medical records. Data on the course and outcome of the disease were obtained through direct contact with patients, their families and their physicians. RESULTS: We registered 161 patients with CMT in the population of Belgrade. The most frequent type was CMT1. The crude prevalence of CMT disease in the Belgrade population on 31 December 2007 was 9.7/100,000 for all subtypes, 7.1/100,000 for CMT1, and 2.3/100,000 for CMT2. Gender-specific prevalence was 11.2/100,000 for males and 8.3/100,000 for females. The highest age-specific prevalence was registered in the oldest age group (75+ years; 19.1/100,000), and the lowest one in patients aged 5-14 years (5.0/100,000). The cumulative probability of 15-year survival for CMT patients in Belgrade was 85.6 ± 7.8% (44.9 ± 31.8% for males and 98.2 ± 1.8% for females). CONCLUSIONS: The prevalence of CMT found in Belgrade is similar to the prevalence registered in Southern European countries.

Psychological well-being in advanced NSCLC patients in Serbia: impact of sociodemographic and clinical factors.

UNLABELLED: Patients with advanced non-small cell lung cancer (NSCLC) usually undergo toxic treatment (chemotherapy and/or radiotherapy). They can experience devastating effects of illness and therapies on their psychological and emotional well-being. On the other hand, untreated psychological distress is associated with reduced quality of life and inadequate palliation of physical symptoms.
In order to estimate frequency of anxiety and depressive symptoms and influence of demographic, socioeconomic and clinical factors on psychological well-being, we performed this cross-sectional study in group of 100 patients with advanced stage of disease. Symptoms of anxiety and depression were assessed using the Hamilton Anxiety Rating Scale (HARS) and Hamilton Depression Rating scale (HDRS). Health-related quality of life data are obtained by EORTC QLC C30 and SF 36.
Patients with poor performance status (PS) experienced significantly more anxiety and depressive symptoms (p=0.001) and worse emotional (p=0.001) and mental functioning (p=0.001). Treated patients had significantly better mental (p=0.011) and emotional (p=0.001) functioning in compared to newly diagnosed ones. Somewhat unusual, unemployed participants reported significantly less anxiety (p=0.029) and depressive (p=0.002) symptoms, better mental (p=0.030) and emotional functioning (p=0.007). Additionally, nausea and vomiting adversely affected mental health and emotional functioning and correlated significantly positively with HARS and HDRS scores.
Our findings suggest significant impact of some disease-related factors (PS, active treatment) and treatment-related factors (chemotherapy -induced nausea and vomiting) on psychological well-being of patients with advanced NSCLC. This should be taking an account when appropriate interventions are planned. KEYWORDS: lung cancer, anxiety, depression, quality of life, chemotherapy, chemotherapy-induced nausea and vomiting.

Validation of Serbian version of the disease-specific myasthenia gravis questionnaire.

AIM: The aim of this study was to validate translated and cross-cultural adapted Italian version of myasthenia gravis-specific questionnaire (MGQ) in Serbian MG patients. MATERIALS AND METHODS: The questionnaire was validated in 140 consecutive MG patients from Belgrade. In each patient association between the total MGQ score and form and severity of the disease was determined. Also, correlation between regional domain scores of MGQ and main clinical findings according to Besinger's clinical score was analyzed. RESULTS: Patients' participation in the assessment was satisfactory with excellent internal consistency and reproducibility. Total MGQ score, as well as domain scores, correlated with highly significant inverse relationship with the disease severity and clinical status of patients at the moment of completing the questionnaire. Furthermore, the bulbar domain of the questionnaire appeared more specific and sensitive than clinical history and examination. CONCLUSION: We concluded that the Serbian version of the MGQ may be useful as a measure of clinical outcome in patients with MG.

Health-related quality of life in lung cancer patients in Serbia: correlation with socio-economic and clinical parameters.

The objective of this study was to assess health-related quality of life (HRQoL) in patients with advanced non-small cell lung cancer (NSCLC). In Serbia, there is the lack of available data on HRQoL in lung cancer patients. The special attention in our study has been paid on relationships between socio-economic factors and HRQoL. This cross-sectional study was undertaken in group of 100 NSCLC patients with advanced stage diseases. HRQoL was measured using three standard instruments: 36-item Short Form Health Survey, EORTC QLQ-C30 and its Lung Cancer module (EORTC QLQ-LC13). Unexpected, highly educated patients reported significantly worse social functioning (P=0.044), and higher degree of financial difficulties (P=0.047), in comparison with less-educated. Also unusual, unemployed patients had significantly better HRQoL in all domains and significantly lower symptom distress. Significantly better overall HRQoL (P=0.043), social (P=0.024), emotional (P=0.001) and mental functioning (P=0.011) were observed in patients treated with chemotherapy in comparison with newly diagnosed ones. In addition, the most prominent side effects of chemotherapy were nausea and vomiting, and all QoL domains correlated significantly with them. Patients who undergo active treatment improve their HRQoL but chemotherapy-induced emesis adversely affects many HRQoL domains. Additionally, HRQoL is highly dependent on patient's socio-economic characteristic.

Do women benefit more from systemic thrombolysis in acute ischemic stroke? A Serbian experience with thrombolysis in ischemic stroke (SETIS) study.

OBJECTIVE: The female sex is associated with increased stroke severity and relatively poor functional recovery. Several studies have demonstrated that women with stroke benefit more from intravenous thrombolysis compared with men, while others found the nullification of gender effect among women treated with recombinant tissue plasminogen activator (rtPA). The purpose of our study was to determine any gender differences in the efficacy and safety of systemic thrombolysis among patients with acute ischemic stroke in Serbia. METHODS: Data were from the Serbian experience with intravenous thrombolysis in ischemic stroke (SETIS) study, a prospective, ongoing, multicenter, open, and observational study in Serbia of all patients who have received rtPA for acute ischemic stroke. We analyzed sex differences in the baseline characteristics, functional outcome and treatment complications. RESULTS: Among 60 women and 96 men with stroke and treated with intravenous thrombolysis, we found that at day 90, no significant sex differences in excellent functional outcome (50.9% of women vs. 57.0% of men, p=0.5), favorable functional outcome (61.4% of women vs. 68.8% of men, p=0.38) or death (8.8% of women vs. 12.9% of men, p=0.60). These results were constant even after adjustments for age, severity of basal neurological deficit and onset to treatment time. CONCLUSION: There were no sex differences in functional outcome at 90 days after the stroke among patients treated with IV rtPA. This finding might confirm that thrombolytic therapy nullifies usual sex differences in stroke outcome and suggests that women with stroke may benefit more from rtPA treatment.

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.

[Pediatric brain tumors--diagnostic and treatment].

During the period 1995-2004 we treated 212 patients (pts) with brain tumors. There were 133 boys and 79 girls, aged from 2,5 yrs up to 18 yrs (Me = 9, 7 yrs). The majority of pts were in age group (4-16) yrs-179 pts. Supratentorial tumors were diagnosed in 118 pts vs. infratentorial 94 pts. Therapy involved surgery, postoperative radiotherapy with or without chemotherapy. Survival rates were calculated using Caplan-Meier method and differences between curves with log-rank test. During the follow-up period from 1 to 9 year (Me = 3 yrs) 5-year disease free survival rate was 55.7%. 79 pts failed to therapy. There was no statistically significant difference in survival according to sex (p = 0.123) and age (p = 0.367). Pts with supratentorial tumors had statistically significant better survival (p = 0.036). Pts with histologic type low grade astrocitomas had statistically significant better survival than malignant gliomas, ependymomas and PNET (p = 0.0001). Surgery, postoperative radiotherapy and chemotherapy in selected cases are efficient therapeutic approach for pediatric brain tumors.