DNAJC13 p.Asn855Ser mutation screening in Parkinson's disease and pathologically confirmed Lewy body disease patients.

BACKGROUND: Recently, a novel mutation in exon 24 of DNAJC13 gene (p.Asn855Ser, rs387907571) has been reported to cause autosomal dominant Parkinson's disease (PD) in a multi-incident Mennonite family. METHODS: In the present study the mutation containing exon of the DNAJC13 gene has been sequenced in a Caucasian series consisting of 1938 patients with clinical PD and 838 with pathologically diagnosed Lewy body disease (LBD). RESULTS: Our sequence analysis did not identify any coding variants in exon 24 of DNAJC13. Two previously described variants in intron 23 (rs200204728 and rs2369796) were observed. CONCLUSION: Our results indicate that the region surrounding the DNAJC13 p.Asn855Ser substitution is highly conserved and mutations in this exon are not a common cause of PD or LBD among Caucasian populations.

Influence of physiotherapy on severity of motor symptoms and quality of life in patients with Parkinson disease.

BACKGROUND AND PURPOSE: Parkinson disease (PD) is one of the most frequent diseases of the central nervous system. Rehabilitation is one of the factors which may help the patients to maintain higher physical activity in everyday life. The aim of this work was to evaluate the influence of movement rehabilitation on severity of motor symptoms in PD patients. MATERIAL AND METHODS: The study included 70 patients suffering from PD according to the Hoehn and Yahr scale. Patients' clinical status was assessed with Unified Parkinson's Disease Rating Scale (UPDRS) parts I-III. Additionally, activity of daily living was evaluated with the Schwab and England scale. The quality of life was evaluated by the Parkinson's Disease Questionnaire (PDQ-39). The examinations were conducted before and after the twelve weeks of the experiment. Patients included in the intervention group (n = 40) took part in 60-minute rehabilitation exercises twice a week, which were aimed at increasing movement ranges, balance improvement, movement agility and walking. The main emphasis was placed on the ability to cope with daily activities. RESULTS: A significant difference in scores of given scales before and after the 12-week period was observed in the intervention group: UPDRS part I score decreased by 17.31%, part II decreased by 22.2%, part III decreased by 18.96%, and PDQ-39 score decreased by 17.12%. Mean score of the Schwab and England scale increased by 9.69%, indicating an improved quality of life. CONCLUSIONS: The applied rehabilitation programme decreased the severity of motor symptoms in patients with PD.

Neck duplex Doppler ultrasound evaluation for assessing chronic cerebrospinal venous insufficiency in multiple sclerosis patients.

INTRODUCTION: Recent clinical studies have suggested a relationship between multiple sclerosis (MS) and the occurrence of pathological changes in the jugular, vertebral and azygous veins that result in abnormal blood outflow from the brain and the spinal cord. Together, these pathological changes have been designated chronic cerebrospinal venous insufficiency (CCSVI). The aim of the present study was to evaluate the usefulness of duplex Doppler ultrasound in the evaluation of central nervous system venous outflow disturbances in patients suffering from MS. METHODS: We examined 181 patients with MS, diagnosed on the basis of the McDonald criteria, and 50 healthy volunteer controls. All patients underwent Doppler ultrasound examination of the internal jugular veins (IJV) and vertebral veins (VVs). The presence of outflow disturbances and morphological abnormalities were evaluated. RESULTS: Pathological changes in the extracranial jugular veins were diagnosed in 148/181 MS patients (82%) and 7/50 control group volunteers (14%). The following abnormalities in the MS group were revealed: the presence of a reflux in the IJVs and/or VVs (54%), narrowing (54%), a complete block in the flow through the IJV (10%) and an abnormal postural control of the cerebral outflow route (25%). These particular pathologies were of statistical significance in the MS group compared with the control group. This study also revealed a correlation between the occurrence of inverted flow in patients in a sitting position and chronic progressive MS (P = 0.0033). CONCLUSIONS: The examinations undertaken indicate a possible connection between MS and CCSVI. The widely accessible and highly sensitive and specific Doppler ultrasound test may be useful for revealing, and preliminary analysis of, CCSVI pathologies.

Intravenous thrombolysis in acute ischemic stroke after POLKARD: one center analysis of program impact on clinical practice.

PURPOSE: Intravenous thrombolysis in the acute ischemic stroke was initiated in Poland within the National Cardiovascular Disease Prevention and Treatment Program POLKARD in the years 2003-2008. Since 2009 the procedure has been reimbursed by the National Health Fund (Narodowy Fundusz Zdrowia - NFZ). The purpose of the presented study was to assess whether the change of financing institution was associated with the change in proportion of patients treated and with any of the clinical parameters or stroke outcomes. PATIENTS AND METHODS: We reviewed the data of the 90 consecutive patients with acute ischemic stroke treated with intravenous thrombolysis within 3-hours from symptoms onset. The differences between the POLKARD period and the year 2009, regarding clinical parameters, time delays, death rates and functional outcomes on day 90 after the stroke were analyzed. The association of outcome measures with baseline characteristics of the patients was analyzed with binary logistic regression. RESULTS: In 2009 there was a significant increase in the proportion of patients treated (7.6%, 95%CI 5.3-10.7%, vs. 4.3%, 95%CI 3.3-5.5% respectively, p=0.013). There were no differences in age, baseline neurological presentation, prevalence of stoke risk factors, treatment time delays or hemorrhagic complications. Higher, but not significantly, 90-day mortality was observed (32.1%, 95%CI 13.3-54.1% vs. 16.1%, 95%CI 6.4-29.7% respectively, p=0.101). Baseline neurological deficits and in-hospital treatment time delays were significant predictors of disability and death. CONCLUSIONS: After the Polish Ministry of Health program POLKARD termination and elimination of the reimbursement limits, higher proportion of ischemic stroke patients could be treated with the intravenous thrombolysis.

Death-associated protein kinase 1 variation and Parkinson's disease.

BACKGROUND AND PURPOSE: Mutations of the LRRK2 gene are now recognized as major risk factors for Parkinson's disease. The Lrrk2 protein is a member of the ROCO family, which also includes Lrrk1 and Dapk1. Functional genetic variants of the DAPK1 gene (rs4877365 and rs4878104) have been previously associated with Alzheimer's disease. METHODS: Herein, we assessed the role of DAPK1 variants (rs4877365 and rs4878104) in risk of Parkinson's disease with Sequenom iPLEX genotyping, employing one Taiwanese series (391 patients with Parkinson's disease, 344 controls) and five separate Caucasian series' (combined sample size 1962 Parkinson's disease patients, 1900 controls). RESULTS: We observed no evidence of association for rs4877365 and rs4878104 and risk of Parkinson's disease in any of the individual series or in the combined Caucasian series under either an additive or recessive model. CONCLUSION: These specific DAPK1 intronic variants do not increase the risk of Parkinson's disease. However, further functional studies are required to elucidate the potential therapeutic implications with the dimerization of the Dapk1 and Lrrk2 proteins.

Cerebral sinus thrombosis as a complication of Crohn's disease: a case report.

Inflammatory bowel disease (IBD) is associated with the occurrence of thrombotic complications. They rarely involve cerebrovascular events, manifesting as arterial ischemic strokes or venous thrombosis, more often in patients with ulcerative colitis than Crohn's disease. Pathogenesis of hypercoagulability in IBD contributing to thromboembolic events is not well known. We present a 31-year old man with Crohn's disease complicated with the transverse and sigmoid sinus thrombosis and secondary intracerebral hemorrhage, confirmed in magnetic resonance imaging. Thrombotic complication occurred during the active phase of the disease and treatment with steroids.

Calbindin-1 association and Parkinson's disease.

BACKGROUND AND PURPOSE: Calcium levels have been proposed to play an important role in the selective vulnerability of nigrostriatal dopaminergic neurons in Parkinson's disease (PD). Recently, an association was reported between the calcium buffer, calbindin (rs1805874) and risk of PD in a Japanese patient-control series. METHODS: We genotyped rs1805874 in four independent Caucasian patient-control series (1543 PD patients, 1771 controls). RESULTS: There was no evidence of an association between rs1805874 and disease risk in individual populations or in the combined series (odds ratio: 1.04, 95% CI: 0.82-1.31, P = 0.74). DISCUSSION: Our study shows there is no association between rs1805874 and risk for PD in four Caucasian populations. This suggests the effect of calbindin on PD risk displays population specificity.

Intravenous recombinant tissue plasminogen activator for acute stroke in Poland: an analysis based on the Safe Implementation of Thrombolysis in Stroke (SITS) Registry.

OBJECTIVES: Intravenous thrombolysis was conditionally approved in the European Union (EU) in 2002, under the requirement of entering all patients into Safe Implementation of Thrombolysis in Stroke - Monitoring Study (SITS-MOST). Countries not belonging to the EU by 2002, i.e. Poland were invited to enter data into the SITS International Stroke Thrombolysis Registry (SITS-ISTR). The aim of this study is to compare the safety and efficacy of thrombolysis in the Polish SITS-ISTR stroke patient population with patients registered in SITS-MOST. METHODS: 481 patients in Poland were reported between 2003 and 2007. Baseline and outcome data of Polish patients were compared with SITS-MOST. RESULTS: Most of the baseline characteristics did not differ between the groups. The most important was the onset-to-needle and door-to-needle times were significantly longer in Polish patients, 150 vs 136 min and 82 vs 68 min, respectively (P < 0.001). The symptomatic intracranial haemorrhage and independence rates at 3 months were similar in both populations. Polish patients had a significantly higher 3-month mortality rate, 18.6% vs 11.3% (P < 0.001). CONCLUSIONS: Because of higher mortality the study implies the need to improve the organization of thrombolysis services and provides the rationale to continue the monitoring of treatment in Poland.

GRN 3'UTR+78 C>T is not associated with risk for Parkinson's disease.

BACKGROUND AND PURPOSE: A single nucleotide polymorphism in the 3'-untranslated region of the progranulin gene (GRN; 3'UTR+78C>T; rs5848) was reported to alter the risk for frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). rs5848 is located within a micro-RNA binding site and affects the expression of GRN. METHODS: As FTLD-U patients often present with parkinsonism, we investigated the association of GRN rs5848 and risk of Parkinson's disease in two Caucasian patient-control series (n = 1413) from the US and Poland. RESULTS: No association was observed between rs5848 and susceptibility to Parkinson's disease (individual series and combined analysis). CONCLUSIONS: This finding shows that GRN rs5848 does not affect the risk of Parkinson's disease in the US and Polish populations.

Interleukin-10 (IL10) and tumor necrosis factor alpha (TNF) gene polymorphisms in Parkinson's disease patients.

Recent studies revealed that inflammatory processes might play an important role in the pathogenesis of Parkinson's disease (PD). We hypothesized that genetically determined differences in the immune response, especially in anti- and pro-inflammatory cytokines production might influence the risk for the development and/or onset of sporadic PD. In the present study, we investigated the genetic polymorphisms of the IL10 (-1082 and -519) and TNF (-308) genes in relation to the risk of PD, and their associations with age of PD onset in a group of 316 patients, divided into two subgroups: Group 1: patients with early onset PD (EOPD), i.e. before 50 years of age (102 patients), and group 2: patients with onset of PD after 50 years of age comprising 214 subjects. Control samples were obtained from 300 randomly selected healthy individuals from the same geographical region with no signs of Parkinsonism as evaluated by a neurologist. PCR-RFLP methods were used for genotyping. No statistically significant differences between PD patients and controls were found in the frequency of a single locus of IL10 promoter. We found TNF -308A allele significantly more frequent in EOPD patients compared to the controls (p=0.007). The overrepresentation of the A allele was reflected by a significant increase in AA homozygous individuals in EOPD patients compared to the controls (p=0.0021). The results from our study revealed that the TNF -308AA genotype might increase the risk of early onset of PD.

Assessment of postural instability in patients with Parkinson's disease.

Postural instability is one of the most disabling features of idiopathic Parkinson's disease (PD). In this study, we focused on postural instability as the main factor predisposing parkinsonians to falls. For this purpose, changes in sway characteristics during quiet stance due to visual feedback exclusion were studied. We searched for postural sway measures that could be potential discriminators for an increased fall risk. A group of 110 subjects: 55 parkinsonians (Hoehn and Yahr: 1-3), and 55 age-matched healthy volunteers participated in the experiment. Their spontaneous sway characteristics while standing quiet with eyes open and eyes closed were analyzed. We found that an increased mediolateral sway and sway area while standing with eyes closed are characteristic of parkinsonian postural instability and may serve to quantify well a tendency to fall. These sway indices significantly correlated with disease severity rated both by the Hoehn and Yahr scale as well as by the Motor Section of the UPDRS. A forward shift of a mean COP position in parkinsonians which reflects their flexed posture was also significantly greater to compare with the elderly subjects and exhibited a high sensitivity to visual conditions. Both groups of postural sway abnormalities identified here may be used as accessible and reliable measures which allow for quantitative assessment of postural instability in Parkinson's disease.

Platelet phospholipase A2 activity in patients with Alzheimer's disease, vascular dementia and ischemic stroke.

Phospholipase A(2) (E.C. 3.1.1.4, PLA(2)) plays an essential role in metabolism of membrane phospholipids, it is related to inflammatory reactions, secretion of amyloid precursor protein and activation of NMDA receptor after ischemia. In the present study we investigated PLA(2) activity in platelets from 37 Alzheimer's disease (AD) patients, 32 vascular dementia (VaD) patients and 32 individuals with ischemic stroke as compared to 27 healthy elderly controls. PLA(2) activity was determined using radiometric assay. Mean platelet PLA(2) activity was increased in individuals with Alzheimer's disease (p < 0.001). In VaD group the enzyme activity was between the values in AD and controls, these differences being significant from both groups. In the group of patients with ischemic stroke mean PLA(2) activity was higher either 48 h after the stroke or 7 days later (in both cases p < 0.001). The results may be particularly interesting in light of the fact, that inhibitors of PLA(2) activity are known.

Polymorphisms of catechol-0-methyltransferase (COMT), monoamine oxidase B (MAOB), N-acetyltransferase 2 (NAT2) and cytochrome P450 2D6 (CYP2D6) gene in patients with early onset of Parkinson's disease.

The aim of the present study was to evaluate the contribution of MAOB, COMT, NAT2 and CYP2D6 gene polymorphisms to early onset Parkinson's disease (PD). The study enrolled 134 patients with Parkinson's disease (early onset-EOPD--67 patients, and late onset--LOPD--patients), and 66 healthy individuals. Polymerane chain reaction restriction fragment length polymorphism (PCR-RFLP) methods were used for genotyping. Univariate analysis revealed a significant two-fold higher EOPD risk among carriers of MAOB allele A or AA genotype. Multivariate analysis revealed that MAOB allele A was an independent factor predisposing to EOPD. It was shown that neither NAT2, CYP2D6 nor COMT genotype was associated with PD.

The effect of monoamine oxidase B (MAOB) and catechol-O-methyltransferase (COMT) polymorphisms on levodopa therapy in patients with sporadic Parkinson's disease.

OBJECTIVES: The etiology of sporadic idiopathic Parkinson's disease (PD) is considered multifactorial with both genetic and environmental factors modifying the disease expression. Recent studies suggest that polymorphism in monoamine oxidase B (MAOB) and catechol-O-methyltransferase (COMT) might influence the risk and treatment of PD. The aim of the study was to evaluate the effect of MAOB and COMT genetic polymorphism on effective daily dose of levodopa applied during the first 5 years of treatment, and to find out if a relationship exists between MAOB and COMT haplotypes and motor disturbances onset in PD patients treated with levodopa preparations. MATERIALS AND METHODS: A total of 95 patients (40 females and 55 males) of Polish origin diagnosed with sporadic PD were enrolled into the study, and were divided into two groups. Group 1 - patients treated with doses of levodopa below 500 mg/day during the first 5 years of treatment. Group 2 - patients requiring levodopa doses exceeding 500 mg/24 h during the first 5 years of treatment. Low activity alleles of MAOB and COMT, i.e. MAOB allele A and COMT(L) as well as high activity ones, i.e. MAOB allele G and COMT(H), were determined using PCR-RFLP method. RESULTS: No statistically significant differences were found in MAOB and COMT allele distribution in the two groups. However, the frequency of COMT(L/L) homozygotes was higher in the group treated with low doses of levodopa when compared with the second group. MAOB and COMT AG-HH haplotype predominated in the group of females treated with high daily doses of levodopa when compared with AG-LL haplotype in the group of females treated with low daily doses of levodopa (<500 mg/24 h). CONCLUSION: The results of the study suggest that patients with COMT(L/L) genotype and possibly MAOB genotype A may benefit from more efficient and safer levodopa therapy.

[Diagnostic problems in the case of dementia with coexisting hematological disorders]. / Trudnosci diagnostyczne w przypadku otepienia ze wspólistniejacymi zaburzeniami hematologicznymi.

The case report presents a 61-year-old female patient with profound dementia and coexisting hematological disorders suggesting Addison-Biermer's disease. Two possible diagnoses were considered; dementia of Alzheimer type or dementia secondary to pernicious anaemia. This case report reflects diagnostic difficulties concerning dementia syndrome in the presence of other causative factors.

[Burden of caregivers caring for persons with dementia]. / Obciazenie opiekunów osób z otepieniem.

Alzheimer's disease (AD) and other dementias are common disorders in the elderly. Most AD patients are cared for at home by family members. Caregiving stress often leads to problems in care givers' mental and physical health. Certain factors predict caregivers' distress, such as the presence of patient behavioral problems, the nature of the caregivers' social support and ability to cope with difficult situations. The term "caregiver burden" is used to refer to the physical, psychological or emotional, social and financial problems that can be experienced by family members caring for impaired older adults.

[The role of carnitine in human lipid metabolism]. / Rola karnityny w przemianie lipidowej u czlowieka.

Carnitine is an important nutrient that is present in diet (particularly in meat and dairy products) and is synthesized from amino acids. Carnitine has two principal functions in the organism. One is to transport long-chain fatty acids into the mitochondrion. The second function of carnitine is to regulate the intramitochondrial ratio of acylocoenzyme A to free coenzyme A. This function is important because it allows to remove excessive (and potentially toxic) short- and medium-chain fatty acids from the mitochondrion, and because it maintains sufficient free coenzyme A within the mitochondrion to support energy metabolism.

The effect of valproic acid on plasma carnitine levels.

Plasma total, free, and acyl carnitine levels were determined in four groups of children: (1) those treated with valproic acid as monotherapy (n = 43), (2) those treated with valproic acid plus other antiepileptics as polytherapy (n = 91), (3) those treated with other antiepileptic drugs alone (n = 43), and (4) normal patients (n = 89). The mean free carnitine level was significantly lower in both the valproic acid monotherapy (29.9 mumol/L) and polytherapy (21.4 mumol/L) groups compared with normal subjects (36.8 mumol/L); it was also significantly lower than that in patients treated with other antiepileptic drugs (36.7 mumol/L). Comparison of valproic acid polytherapy and monotherapy yielded significantly lower free carnitine levels in the polytherapy group. The ratios of acyl to free carnitine for monotherapy (0.41) and polytherapy (0.45) were significantly higher than that in the normal group (0.25). This study indicates that a general decrease in the carnitine pool should be anticipated in patients taking valproic acid polytherapy and, to a lesser degree, monotherapy. Carnitine levels in the group taking other drugs did not differ from normal.

[Etiology, occurrence and types of the internal carotid artery loop]. / Etiologia, czestosc wystepowania i typy uksztaltowania petli naczynio-wej w przebiegu tetnicy szyjnej wewnetrznej.

Internal carotid loop was studied in 99 patients out of 1638 cases subjected to angiography. The presence of a loop was arbitrarily accepted when in the tortuous part of the artery one of its segments was situated below the preceding segment. For the spatial analysis of the tortuous part of the artery and its image in the plane of the radiogram a model was used simulating various variants of the course of the internal carotid artery. On the ground of the analysis of the spatial configuration of the arterial loops and the variability of the loop model in the plane of the radiogram six types of the loop were isolated. The loops were found in 9.2% of patients with bilateral angiography and 5.7% of those with unilateral angiography. In adults the loop was present in 5.4% of cases, and in children in 8.9% (statistically significant difference p less than 0.05). It is assumed that the loop in children is a congenital anomaly, while in adulthood besides the congenital etiology an acquired form of the loop is to be taken into account.