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Idiopathic PD (idiopathic + pd)
Selected AbstractsMRI verified STN stimulation site , gait improvement and clinical outcomeEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2010E. L. Johnsen Background:, Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in alleviating Parkinson's disease (PD) symptoms (tremor, rigidity and bradykinesia) and may improve gait and postural impairment associated with the disease. However, improvement of gait is not always as predictable as the clinical outcome. This may relate to the type of gait impairment or localization of the active DBS contact. Methods:, The active contact was visualized on peri-operative magnetic resonance imaging in 22 patients with idiopathic PD, consecutively treated with bilateral STN DBS. Stimulation site was grouped as either in the dorsal/ventral STN or medial/lateral hereof and anterior/posterior STN or medial/lateral hereof. The localization was compared with relative improvement of clinical outcome (UPDRS-III). In 10 patients, quantitative gait analyses were performed, and the improvement in gait performance was compared with stimulation site in the STN. Results:, Of 44 active contacts, 77% were inside the nucleus, 23% were medial hereof. Stimulation of the dorsal half improved UPDRS-III significantly more than ventral STN DBS (P = 0.02). However, there were no differences between anterior and posterior stimulation in the dorsal STN. Step velocity and length improved significantly more with dorsal stimulation compared with ventral stimulation (P = 0.03 and P = 0.02). Balance during gait was also more improved with dorsal stimulation compared with ventral stimulation. Conclusions:, Deep brain stimulation of the dorsal STN is superior to stimulation of the ventral STN. Possible different effects of stimulation inside the nucleus underline the need for exact knowledge of the active stimulation site position to target the most effective area. [source] Chronic high dose transdermal nicotine in Parkinson's disease: an open trialEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2007G. Villafane Whether nicotine has therapeutic effects on Parkinson's disease (PD) symptoms is controversial, but high doses and chronic treatment have never been tested. We report the results of a pilot, open-label trial to assess the safety and possible efficacy of chronic high doses of nicotine. Six patients with advanced idiopathic PD received increasing daily doses of transdermal nicotine up to 105 mg/day over 17 weeks. All patients but one accepted the target dose. Nausea and vomiting were frequent but moderate, and occurred in most of the patients (four of six) who received over 90 mg/day and 14 weeks of nicotine treatment. During the plateau phase, patients improved their motor scores and dopaminergic treatment was reduced. These results confirm the feasibility of chronic high dose nicotinic treatment in PD but warrant validation of the beneficial effects by a randomized controlled trial. [source] Rasagiline: defining the role of a novel therapy in the treatment of Parkinson's diseaseINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2006F. Stocchi Summary Parkinson's disease (PD) is a therapy area with considerable unmet needs. The current key targets for PD treatment include the slowing of disease progression, improved control of motor fluctuations in advanced disease and the treatment of nonmotor symptoms. In view of such major requirements, it is important to consider how new drug treatments fit into the context of PD therapy, and the practical advantages that they may offer in the management of PD in clinical practice. Rasagiline is a novel, second-generation, irreversible, selective monoamine oxidase type B inhibitor that is indicated for the treatment of idiopathic PD, either as initial monotherapy or as adjunct therapy (with levodopa) for patients experiencing end-of-dose motor fluctuations. This review assesses the outcome from several large-scale clinical studies that have investigated the use of rasagiline in early and advanced PD patient populations and discusses the role of rasagiline within the current scope of PD therapy. [source] Diagnostic and therapeutic value of apomorphine in Parkinsonian patientsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2004J.C. Sharma Summary Apomorphine is a dopamine agonist administered subcutaneously for the management of motor symptoms of Parkinson's disease (PD). Patients with Parkinsonian syndrome underwent an apomorphine challenge for therapeutic efficacy, a positive response being a reduction of >15% score on motor unified PD rating scale. Of the 42 patients, aged 37,81, disease duration 12 months to 20 years, 36 had a positive response. Six non-responders were later diagnosed as non-PD as compared with only two of the 36 responders. Tremor-predominant patients obtained higher motor response. Few patients demonstrated a delayed positive response. Seven (three idiopathic PD (iPD), four non-PD) suffered adverse reactions of nausea, vomiting or ill-sustained symptomatic fall in BP. Majority of the patients who continued with apomorphine therapy were able to reduce levodopa and achieved an improvement in dyskinesia and motor symptoms. Thirteen responding patients were managed by increasing dopamine agonists. Five patients, intolerant of oral dopamine agonists, were able to beneficially tolerate apomorphine. Age and disease duration did not influence tolerability or efficacy. The patients treated with apomorphine were able to significantly reduce the dose of levodopa, and there was a reduction in dyskinesia, hallucinations and fluctuations (all p < 0.05). In some patients, apomorphine prevented admission to institutions. We also describe the use of apomorphine in acutely ill patients unable to ingest oral medication. Apomorphine seems to have a diagnostic element for iPD. Its use leads to a reduction in dyskinesia, improvement in motor symptoms and prevention of institutional care. Apomorphine test also identifies patients likely to benefit with an increase in oral medication. Age and disease duration should not prevent the use of this valuable drug. Apomorphine also has a role in acutely ill PD patients. [source] Effect of Psychiatric and Other Nonmotor Symptoms on Disability in Parkinson's DiseaseJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2004Daniel Weintraub MD Objectives: To examine the effect of depression and other nonmotor symptoms on functional ability in Parkinson's disease (PD). Design: A cross-sectional study of a convenience sample of PD patients receiving specialty care. Setting: The Parkinson's Disease Research, Education and Clinical Center at the Philadelphia Veterans Affairs Medical Center. Participants: One hundred fourteen community-dwelling patients with idiopathic PD. Measurements: The Unified Parkinson's Disease Rating Scale (UPDRS); Hoehn and Yahr Stage; Mini-Mental State Examination; Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, depression module; probes for psychotic symptoms; Hamilton Depression Rating Scale; Geriatric Depression Scale,Short Form; Apathy Scale; and Epworth Sleepiness Scale. Disability was rated using the UPDRS activity of daily living (ADL) score and the Schwab and England ADL score. Multivariate analysis determined effect of depression and other nonmotor symptoms on disability. Results: The presence of psychosis, depressive disorder, increasing depression severity, age, duration of PD, cognitive impairment, apathy, sleepiness, motor impairment, and percentage of time with dyskinesias were related to greater disability in bivariate analyses. Entering these factors into two multiple regression analyses, only the increasing severity of depression and worsening cognition were associated with greater disability using the UPDRS ADL score, accounting for 37% of the variance in disability (P<.001). These two factors plus increasing severity of PD accounted for 54% of the variance in disability using the Schwab and England ADL score (P<.001). Conclusion: Results support and extend previous findings that psychiatric and other nonmotor symptoms contribute significantly to disability in PD. Screening for nonmotor symptoms in PD is necessary to more fully explain functional limitations. Further study is required to determine whether identifying and treating these symptoms will improve function and quality of life. [source] Biochemical aspects of the neuroprotective mechanism of PTEN-induced kinase-1 (PINK1)JOURNAL OF NEUROCHEMISTRY, Issue 1 2008Ryan D. Mills Abstract Mutations in PTEN-induced kinase 1 (PINK1) gene cause PARK6 familial Parkinsonism. To decipher the role of PINK1 in pathogenesis of Parkinson's disease (PD), researchers need to identify protein substrates of PINK1 kinase activity that govern neuronal survival, and establish whether aberrant regulation and inactivation of PINK1 contribute to both familial Parkinsonism and idiopathic PD. These studies should take into account the several unique structural and functional features of PINK1. First PINK1 is a rare example of a protein kinase with a predicted mitochondrial-targeting sequence and a possible resident mitochondrial function. Second, bioinformatic analysis reveals unique insert regions within the kinase domain that are potentially involved in regulation of kinase activity, substrate selectivity and stability of PINK1. Third, the C-terminal region contains functional motifs governing kinase activity and substrate selectivity. Fourth, accumulating evidence suggests that PINK1 interacts with other signaling proteins implicated in PD pathogenesis and mitochondrial dysfunction. The most prominent examples are the E3 ubiquitin ligase Parkin, the mitochondrial protease high temperature requirement serine protease 2 and the mitochondrial chaperone tumor necrosis factor receptor-associated protein 1. How PINK1 may regulate these proteins to maintain neuronal survival is unclear. This review describes the unique structural features of PINK1 and their possible roles in governing mitochondrial import, processing, kinase activity, substrate selectivity and stability of PINK1. Based upon the findings of previous studies of PINK1 function in cell lines and animal models, we propose a model on the neuroprotective mechanism of PINK1. This model may serve as a conceptual framework for future investigation into the molecular basis of PD pathogenesis. [source] MAPK-pathway activity, Lrrk2 G2019S, and Parkinson's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2007Linda R. White Abstract The 6055G>A mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in a G2019S substitution in the mixed-lineage kinase domain of Lrrk2, causing autosomal dominant Parkinson's disease (PD). We hypothesized the mutation alters cellular mitogen-activated protein kinase (MAPK) signalling cascades, and might be detectable in tissues other than in the brain. We therefore compared total levels and activation of the signalling proteins Src, HSP27, p38 MAPK, JNK, and ERK, in extracts of leukocytes isolated from patients with PD carrying the G2019S mutation, healthy mutation carriers, patients with idiopathic PD, and healthy controls. Phosphorylation of Src, HSP27, and JNK was reduced significantly in cell extracts from patients with G2019S-associated PD compared to healthy controls. Similarly, phosphorylation was reduced significantly in Src and HSP27 in the group of healthy carriers of the mutation, as well as in patients with idiopathic PD. Significant reductions in total Src were also observed in these three groups compared to the controls. The results of this pilot project therefore indicate significant alterations in key signalling proteins in leukocytes from patients with PD, and were most pronounced in G2019S-associated PD. Changes in MAPK-signalling may thus be common to PD pathophysiology, regardless of aetiology. Such changes may also be shown in blood samples during the preclinical stage of LRRK2 -associated PD, which could be particularly important for the development of neuroprotective strategies to delay onset, or slow progression of PD. © 2007 Wiley-Liss, Inc. [source] Kinematic study of whole body center of mass position during gait in Parkinson's disease patients with and without festination,MOVEMENT DISORDERS, Issue 6 2010Marcelo Merello MD Abstract Gait festination (FE) can cause serious disability in Parkinson's disease (PD) patients. It is argued that the center of pressure position (COP) and body center of mass (COM) are possibly implicated in FE pathogenesis. The relationship between them remains unclear. The goal of this study was to determine spatiotemporal relationships between COM and COP in PD and to explore whether FE arises as a consequence of lack of physiological link between COP and COM during step stride. Twenty patients with idiopathic PD, in OFF state and 17-age-matched control subjects completed a 10-m walking protocol. PD patients were divided in two groups: those with FE and those without (NF). COM position, excursion, and its relationship with COP, as well as other kinematic parameters were analyzed. COM displacement along the horizontal and vertical plane was significantly lower in FE patients as was the maximum position on the movement direction axis compared with controls or NF patients. Significant difference in minimal COM position in FE patients was also observed. The percentage of stride time during which COM was situated ahead of COP along the movement axis in FE patients was significantly greater than for controls or NF patients. This would seem to indicate that FE patients are constantly attempting to align COP to COM, causing FE. The explanation might be that FE arises as a postural strategy to align COP within the area of COM displacement. Findings illustrate a putative role for postural strategies in the treatment of FE. © 2010 Movement Disorder Society [source] Motor laterality asymmetry and nonmotor symptoms in Parkinson's disease,MOVEMENT DISORDERS, Issue 1 2010Esther Cubo Abstract Background: In patients with Parkinson's disease (PD), asymmetric motor signs provide an interesting model to evaluate whether asymmetric nigrostriatal degeneration can affect neuropsychological function and other nonmotor symptoms (NMS). This study was designed to evaluate the predominant laterality of motor symptoms and its relationship with cognition and other NMS in idiopathic PD. Methods: Nationwide, longitudinal, and multicenter study (ELEP Registry) using outpatients with PD. Left PD (LPD) and right PD (RPD) was defined based on the motor signs on the SCOPA-motor scale. To include the clinical spectrum of asymmetric PD patients, we considered two groups of patients with mild-moderate and extreme asymmetry. Predominant LPD or RPD with mild-moderate versus extreme asymmetry were compared using the following scales: cognition, psychosis (Parkinson Psychosis Rating Scale), anxiety/depression, sleep (and autonomic dysfunction at baseline and 1 year later. Nonparametric tests were used for comparison. Results: One hundred forty-nine PD patients (74 RPD and 75 LPD) with mild-moderate asymmetry and 90 (47 RPD and 43 LPD) with extreme asymmetry and a mean age of 64.5 (10.4) years were included. Extreme RPD had higher Parkinson Psychosis Rating Scale scores over time (P = 0.005) compared with LPD, but no significant differences were observed between LPD and RPD in terms of other NMS. Conclusions: These findings suggest that damage to left-hemisphere plays a disproportionately greater role in PD-related psychosis over time. In contrast, motor laterality does not consistently affect other NMS, suggesting that NMS are related to a more widespread brain disorder. © 2009 Movement Disorder Society [source] Nigrostriatal dysfunction in homozygous and heterozygous parkin gene carriers: An 18F-dopa PET progression study,MOVEMENT DISORDERS, Issue 15 2009Nicola Pavese MD Abstract Little is known about the rate of progression of striatal dysfunction in subjects with parkin -linked parkinsonism. Being a heterozygous parkin gene carrier may confer susceptibility to Parkinson's disease (PD). In a previous 18F-dopa PET study, we reported that 69% of carriers of a single parkin mutation showed subclinical loss of putamen dopaminergic function. Using serial 18F-dopa PET, the present longitudinal study addresses rates of progression of nigrostriatal dysfunction in both compound heterozygous (parkin -linked parkinsonism) and single heterozygous parkin gene carriers. Three symptomatic patients who were compound heterozygotes for parkin gene mutations and six asymptomatic heterozygous carriers were clinically assessed and had 18F-dopa PET at baseline and again after 5 years. The patients with symptomatic parkin showed a mean 0.5% annual reduction in putamen 18F-dopa uptake over 5 years while caudate 18F-dopa uptake declined by a mean annual rate of 2 %. The asymptomatic heterozygote gene carriers showed a mean 0.56% annual reduction in putamen and 0.62 % annual reduction in caudate 18F-dopa uptake. Neurological examination at both baseline and follow-up showed no evidence of parkinsonism. Loss of nigrostriatal dysfunction in parkin -linked parkinsonism occurs at a very slow rate compared to the 9,12% annual loss of putamen 18F-dopa uptake reported for idiopathic PD. Although subclinical reductions of striatal 18F-dopa uptake are common in carriers of a single parkin mutation their slow rate of progression suggests that few if any of these will develop clinical parkinsonism. © 2009 Movement Disorder Society [source] A novel LRRK2 mutation in an Austrian cohort of patients with Parkinson's diseaseMOVEMENT DISORDERS, Issue 11 2007Dietrich Haubenberger MD Abstract To investigate the frequency of mutations in the Leucine-Rich Repeat Kinase 2 gene (LRRK2) in a sample of Austrian Parkinson's disease (PD) patients, we sequenced the complete coding region in 16 patients with autosomal dominant PD. Furthermore, we sequenced exons 31, 35, and 41 additionally in 146 patients with idiopathic PD and 30 patients with dementia with Lewy bodies. Furthermore, all 192 patients were screened for 21 putative LRRK2 mutations. While the most common mutation G2019S and the risk variant G2385R were not found in our samples, we detected a novel missense mutation (S973N) in a patient with familial, late-onset and dopa-responsive PD. © 2007 Movement Disorder Society [source] Parkinson's disease and LRRK2: Frequency of a common mutation in U.S. movement disorder clinicsMOVEMENT DISORDERS, Issue 4 2006Denise M. Kay PhD Abstract The G2019S mutation in the LRRK2 gene is reportedly a common cause of familial Parkinson's disease (PD) and may also have a significant role in nonfamilial PD. The objective of this study was to assess mutation carrier frequency in PD patients from movement disorder clinics in the United States, stratified by family history, age at onset, and geography; to determine carrier frequency in a large and well-characterized control population; to examine segregation of mutation in families of patients; and to correlate genotype with clinical phenotype. One thousand four hundred twenty-five unrelated PD patients from movement disorder clinics in Oregon, Washington, and New York and 1,647 unrelated controls were studied. The G2019S mutation was detected using a TaqMan assay and verified by sequencing. Eighteen of 1,425 patients and one of 1,647 controls had the mutation. Carrier frequency (± 2SE) in patients was 0.013 ± 0.006 overall, 0.030 ± 0.019 in familial PD, 0.007 ± 0.005 in nonfamilial PD, 0.016 ± 0.013 in early-onset PD, and 0.012 ± 0.007 in late-onset PD. Geographic differences were insignificant. Age at onset of mutation carriers ranged from 28 to 71 years. Mutation carriers were clinically indistinguishable from idiopathic PD. LRRK2 G2019S is the single most common pathogenic mutation linked to neurodegenerative disease to date. © 2005 Movement Disorder Society [source] Double-blind, placebo-controlled study to evaluate the efficacy and safety of botulinum toxin type A in the treatment of drooling in parkinsonismMOVEMENT DISORDERS, Issue 6 2003Francesca Mancini MD Abstract Drooling is a frequent symptom in Parkinson's disease (PD), occurring in almost 75% of all patients. Although it is now well known that drooling in PD is the result of swallowing difficulties rather than excessive saliva production, few treatments have been developed to reduce it. Clinical studies suggest that botulinum toxin A (BTX) injections into salivary glands are effective in decreasing drooling in PD patients. In this double-blind, placebo-controlled study, 20 patients with parkinsonism (idiopathic PD or multiple system atrophy), were randomly assigned to receive 450 U of BTX (Dysport; Ipsen, Berkshire, UK) or 2 ml of placebo, injected into the parotids and submandibular glands under ultrasonographic guidance. Treatment efficacy and safety were assessed at baseline, 1 week and 3 months after BTX injections using clinical scales (Drooling Severity and Drooling Frequency scales) and side effects surveillance. After treatment, the average secretion of saliva in the BTX group was significantly lower than in the placebo group, as appraised by clinical measurements. No side effects were observed in either group. BTX injection into parotids and submandibular glands, under ultrasonographic guidance, is an effective and safe treatment for drooling in parkinsonism. © 2003 Movement Disorder Society [source] Review: Familial Parkinson's disease , genetics, clinical phenotype and neuropathology in relation to the common sporadic form of the diseaseNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2008Carola Schiesling The identification of the first gene in familial Parkinson's disease (PD) only 10 years ago was a major step in the understanding of the molecular mechanisms in neurodegeneration. Alpha-synuclein aggregation was not only recognized as a key event in neurodegeneration in patients carrying mutations in this gene, but it turned out to be the most consistent marker to define Lewy body pathology also in non-heritable idiopathic PD (IPD). Subsequent comprehensive pathoanatomical studies of IPD brains led to a novel concept of an ascending pathological process in variable stages that are reflected by alpha-synuclein aggregation at specific predilection sites. To date, more than seven genes are known to cause familial PD. The fact that these genetic forms of Parkinsonism present with clinical features indistinguishable from IPD, but may display neuropathological features that are not consistent with IPD, underscores the need of a more differentiated approach to familial and sporadic forms of Parkinsonism. Indeed, in distinct populations, mutations in one single gene were found to cause the disease in up to 40% of patients formerly described as ,idiopathic' cases. These findings indicate that IPD, as defined by a late-onset disorder with no (apparent) genetic contribution, is part of a clinical syndrome that becomes more and more heterogeneous in terms of aetiology, with overlapping clinical and pathoanatomical features. Thus in the present review, we discuss clues from familial PD to our understanding of the molecular pathogenesis of neurodegeneration with special consideration of the variable clinical and neuropathological aspects. [source] LRRK2 is a component of granular alpha-synuclein pathology in the brainstem of Parkinson's diseaseNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2008J. Alegre-Abarrategui Classical Parkinson's disease (PD) is characterized by the appearance of Lewy bodies (LBs) in affected brain regions, showing mostly compact alpha-synuclein deposition, in contrast with punctate or granular deposition, hypothesized to represent early stages of aggregation. Leucine-rich repeat kinase 2 (LRRK2) is the commonest mutated gene in inherited and idiopathic PD. LRRK2 mutation carriers display a diverse neuropathology, including alpha-synuclein and tau inclusions, suggesting an upstream role for LRRK2 in protein aggregation. We studied LRRK2 expression throughout the normal human brain with three different antibodies. We also examined the pattern of LRRK2 expression in relation to alpha-synuclein aggregation and LB formation in the brainstem of sporadic LB disease. Physiological LRRK2 expression was not restricted to regions preferentially affected in PD and LRRK2 often localized to the nuclear envelope in addition to the known cytoplasmic expression. In PD, we were able to consistently detect LRRK2 in the halo of a minority (approximately 10%) of nigral LBs using three different antibodies. Only one antibody detected LRRK2 in the core of approximately 80% of classic LBs. In the lower brainstem, most notably in the dorsal motor nucleus of the vagus, we found previously unrecognized LRRK2 labelling of complex globular lesions, filled with LB-like matter showing a punctate or granular staining for alpha-synuclein. This was often accompanied by strong LRRK2 expression within dystrophic neurites. Our findings confirm widespread physiological LRRK2 expression in the human brain and suggest an association of LRRK2 with possible early-stage alpha-synuclein pathology in the brainstem of PD. [source] First appraisal of brain pathology owing to A30P mutant alpha-synucleinANNALS OF NEUROLOGY, Issue 5 2010Kay Seidel PhD Familial Parkinson disease (PD) due to the A30P mutation in the SNCA gene encoding alpha-synuclein is clinically associated with PD symptoms. In this first pathoanatomical study of the brain of an A30P mutation carrier, we observed neuronal loss in the substantia nigra, locus coeruleus, and dorsal motor vagal nucleus, as well as widespread occurrence of alpha-synuclein immunopositive Lewy bodies, Lewy neurites, and glial aggregates. Alpha-synuclein aggregates ultrastructurally resembled Lewy bodies, and biochemical analyses disclosed a significant load of insoluble alpha-synuclein, indicating neuropathological similarities between A30P disease patients and idiopathic PD, with a more severe neuropathology in A30P carriers. ANN NEUROL 2010;67:684,689 [source] Single-cell expression profiling of dopaminergic neurons combined with association analysis identifies pyridoxal kinase as Parkinson's disease gene,ANNALS OF NEUROLOGY, Issue 6 2009Matthias Elstner MD Objective The etiology of Parkinson disease (PD) is complex and multifactorial, with hereditary and environmental factors contributing. Monogenic forms have provided molecular clues to disease mechanisms but genetic modifiers of idiopathic PD are still to be determined. Methods We carried out whole-genome expression profiling of isolated human substantia nigra (SN) neurons from patients with PD vs. controls followed by association analysis of tagging single-nucleotide polymorphisms (SNPs) in differentially regulated genes. Association was investigated in a German PD sample and confirmed in Italian and British cohorts. Results We identified four differentially expressed genes located in PD candidate pathways, ie, MTND2 (mitochondrial, p = 7.14 × 10,7), PDXK (vitamin B6/dopamine metabolism, p = 3.27 × 10,6), SRGAP3 (axon guidance, p = 5.65 × 10,6), and TRAPPC4 (vesicle transport, p = 5.81 × 10,6). We identified a DNA variant (rs2010795) in PDXK associated with an increased risk of PD in the German cohort (p = 0.00032). This association was confirmed in the British (p = 0.028) and Italian (p = 0.0025) cohorts individually and reached a combined value of p = 1.2 × 10,7 (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.18,1.44). Interpretation We provide an example of how microgenomic genome-wide expression studies in combination with association analysis can aid to identify genetic modifiers in neurodegenerative disorders. The detection of a genetic variant in PDXK, together with evidence accumulating from clinical studies, emphasize the impact of vitamin B6 status and metabolism on disease risk and therapy in PD. Ann Neurol 2009;66:792,798 [source] ,-Synuclein promoter confers susceptibility to Parkinson's diseaseANNALS OF NEUROLOGY, Issue 4 2004Philippe Pals MD Familial Parkinson's disease (PD) has been linked to missense and genomic multiplication mutations of the ,-synuclein gene (SNCA). Genetic variability within SNCA has been implicated in idiopathic PD in many populations. We now confirm and extend these findings, within a Belgian sample, using a high-resolution map of genetic markers across the SNCA locus. Our study implicates the SNCA promoter in susceptibility to PD, and more specifically defines a minimum promoter haplotype, spanning approximately 15.3kb of sequence, which is overrepresented in patients. Our findings represent a biomarker for PD and may have implications for patient diagnosis, longitudinal evaluation, and treatment. Ann Neurol 2004;56:591,595 [source] Psychiatric morbidity in patients with Parkinson's disease following bilateral subthalamic deep brain stimulation: literature reviewACTA NEUROPSYCHIATRICA, Issue 4 2008Linton J. Meagher Objective:, To provide a comprehensive review and evaluation of the literature pertaining to the psychiatric sequelae of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). Methods:, A structured search of the EMBASE, PsychINFO and MEDLINE databases was performed on articles published since the first use of STN DBS in 1993 for PD until March 2007. Non-human studies were excluded, along with studies reporting on unilateral DBS and studies reporting on the use of STN DBS for indications other than idiopathic PD. Ninety-seven articles were selected for inclusion in the review. Results:, Patients with advanced PD have a high rate of psychiatric morbidity. STN DBS has been shown to be an effective treatment for the control of motor symptoms in advanced PD. Neurobehavioural side-effects are, however, relatively common following STN DBS. Side-effects include impaired executive function and verbal fluency, depression, hypomania, apathy, postoperative delirium, anxiety disorders and psychotic symptoms, especially hallucinations. The alteration in dopaminergic medication following surgery as well as the direct effect of STN stimulation both appear to contribute to the short-term and long-term postoperative psychiatric complications. Methodological issues that limit the applicability of the current literature in this field are highlighted. Conclusions:, STN DBS is an effective treatment for the motor symptoms of advanced PD. However, further research is needed to assess the extent to which STN DBS contributes to or exacerbates psychiatric morbidity over and above that associated with advanced PD. Careful neuropsychiatric evaluation and monitoring are required in this patient group. [source] | |||||||||||||