47 results on '"Bentivoglio, Anna Rita"'
Search Results
2. Prevalence of spinocellulart ataxia type 2 mutation among ittalian Parkinsonian patients
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Modoni, Antonio, Contarino, Maria Fiorella, Bentivoglio, Anna Rita, Tabolacci, Elisabetta, Santoro, Marco, Calcagni, Maria Lucia, Tonali, Pietro Attilio, Neri, Giovanni, and Silvestri, Gabriella
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Datscan ,SPECT ,Parkinson ,Settore MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA - Published
- 2007
3. Phenotypic characterisation of DYT13 primary torsion distonia
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Bentivoglio, Anna Rita, Ialongo, Tamara, Contarino, Maria Fiorella, Valente, Enza Maria, and Albanese, Alberto
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Settore MED/26 - NEUROLOGIA ,Parkinson - Published
- 2004
4. An MDS Evidence-Based Review on Treatments for Huntington's Disease.
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Ferreira JJ, Rodrigues FB, Duarte GS, Mestre TA, Bachoud-Levi AC, Bentivoglio AR, Burgunder JM, Cardoso F, Claassen DO, Landwehrmeyer GB, Kulisevsky J, Nirenberg MJ, Rosser A, Roth J, Seppi K, Slawek J, Furr-Stimming E, Tabrizi SJ, Walker FO, Vandenberghe W, Costa J, and Sampaio C
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- Humans, Tetrabenazine therapeutic use, Apathy, Chorea, Huntington Disease drug therapy, Huntington Disease therapy, Movement Disorders drug therapy
- Abstract
Background: Huntington's disease (HD) is a rare neurodegenerative disorder with protean clinical manifestations. Its management is challenging, consisting mainly of off-label treatments., Objectives: The International Parkinson and Movement Disorder Society commissioned a task force to review and evaluate the evidence of available therapies for HD gene expansion carriers., Methods: We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Eligible randomized controlled trials were identified via an electronic search of the CENTRAL, MEDLINE, and EMBASE databases. All eligible trials that evaluated one or more of 33 predetermined clinical questions were included. Risk of bias was evaluated using the Cochrane Risk of Bias tool. A framework was adapted to allow for efficacy and safety conclusions to be drawn from the balance between the GRADE level of evidence and the importance of the benefit/harm of the intervention., Results: Twenty-two eligible studies involving 17 interventions were included, providing data to address 8 clinical questions. These data supported a likely effect of deutetrabenazine on motor impairment, chorea, and dystonia and of tetrabenazine on chorea. The data did not support a disease-modifying effect for premanifest and manifest HD. There was no eligible evidence to support the use of specific treatments for depression, psychosis, irritability, apathy, or suicidality. Similarly, no evidence was eligible to support the use of physiotherapy, occupational therapy, exercise, dietary, or surgical treatments., Conclusions: Data for therapeutic interventions in HD are limited and support only the use of VMAT2 inhibitors for specific motor symptoms. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)
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- 2022
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5. GBA-Related Parkinson's Disease: Dissection of Genotype-Phenotype Correlates in a Large Italian Cohort.
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Petrucci S, Ginevrino M, Trezzi I, Monfrini E, Ricciardi L, Albanese A, Avenali M, Barone P, Bentivoglio AR, Bonifati V, Bove F, Bonanni L, Brusa L, Cereda C, Cossu G, Criscuolo C, Dati G, De Rosa A, Eleopra R, Fabbrini G, Fadda L, Garbellini M, Minafra B, Onofrj M, Pacchetti C, Palmieri I, Pellecchia MT, Petracca M, Picillo M, Pisani A, Vallelunga A, Zangaglia R, Di Fonzo A, Morgante F, and Valente EM
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- Dissection, Genotype, Glucosylceramidase genetics, Humans, Italy epidemiology, Mutation genetics, Phenotype, Parkinson Disease epidemiology, Parkinson Disease genetics
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Background: Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD). The impact of different variants on the PD clinical spectrum is still unclear., Objectives: We determined the frequency of GBA-related PD in Italy and correlated GBA variants with motor and nonmotor features and their occurrence over time., Methods: Sanger sequencing of the whole GBA gene was performed. Variants were classified as mild, severe, complex, and risk. β-glucocerebrosidase activity was measured. The Kaplan-Meier method and Cox proportional hazard regression models were performed., Results: Among 874 patients with PD, 36 variants were detected in 14.3%, including 20.4% early onset. Patients with GBA-PD had earlier and more frequent occurrence of several nonmotor symptoms. Patients with severe and complex GBA-PD had the highest burden of symptoms and a higher risk of hallucinations and cognitive impairment. Complex GBA-PD had the lowest β-glucocerebrosidase activity., Conclusions: GBA-PD is highly prevalent in Italy. Different types of mutations underlie distinct phenotypic profiles. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)
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- 2020
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6. Idiopathic Non-task-Specific Upper Limb Dystonia, a Neglected Form of Dystonia.
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Defazio G, Ercoli T, Erro R, Pellicciari R, Mascia MM, Fabbrini G, Albanese A, Lalli S, Eleopra R, Barone P, Marchese R, Ceravolo R, Scaglione C, Liguori R, Esposito M, Bentivoglio AR, Bertolasi L, Altavista MC, Bono F, Pisani A, Girlanda P, and Berardelli A
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- Adult, Female, Humans, Italy, Male, Retrospective Studies, Tremor, Dystonia, Dystonic Disorders
- Abstract
Objective: The objective of this study was to describe the clinical and demographic features of idiopathic non-task-specific upper limb dystonia compared with the task-specific form., Methods: In this retrospective study, adult patients with idiopathic upper limb dystonia, either focal or as part of a segmental/multifocal dystonia, from the Italian Dystonia Registry were enrolled. In patients with focal upper limb dystonia, dystonia spread was estimated by survival analysis., Results: Of the 1522 patients with idiopathic adult-onset dystonia included in the Italian Dystonia Registry, we identified 182 patients with upper limb dystonia. Non-task-specific dystonia was present in 61.5% of enrolled cases. Women predominated among non-task-specific patients, whereas men predominated in the task-specific group. Peak age of upper limb dystonia onset was in the sixth decade in the non-task-specific group and in the fourth decade in the task-specific group. In both groups, upper limb dystonia started as focal dystonia or as part of a segmental dystonia. Segmental onset was more frequent among non-task-specific patients, whereas focal onset predominated among task-specific patients. Dystonic action tremor was more frequent among non-task-specific patients. No significant differences between groups emerged in terms of sensory trick frequency, rest tremor, or family history of dystonia. In patients with focal upper limb dystonia, dystonia spread was greater in the non-task-specific group., Conclusion: Novel information on upper limb dystonia patients suggests that non-task-specific and task-specific upper limb dystonia have different demographic and clinical features. However, it remains to be determined whether these differences also reflect pathophysiological differences. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)
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- 2020
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7. Frequency and phenotypic spectrum of KMT2B dystonia in childhood: A single-center cohort study.
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Carecchio M, Invernizzi F, Gonzàlez-Latapi P, Panteghini C, Zorzi G, Romito L, Leuzzi V, Galosi S, Reale C, Zibordi F, Joseph AP, Topf M, Piano C, Bentivoglio AR, Girotti F, Morana P, Morana B, Kurian MA, Garavaglia B, Mencacci NE, Lubbe SJ, and Nardocci N
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- Adolescent, Adult, Aged, Child, Cohort Studies, Deep Brain Stimulation methods, Female, Humans, Intellectual Disability genetics, Male, Middle Aged, Mutation genetics, Phenotype, Young Adult, Dystonic Disorders genetics, Histone-Lysine N-Methyltransferase genetics
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Background: Childhood-onset dystonia is often genetically determined. Recently, KMT2B variants have been recognized as an important cause of childhood-onset dystonia., Objective: To define the frequency of KMT2B mutations in a cohort of dystonic patients aged <18 years at onset, the associated clinical and radiological phenotype, and the natural history of disease., Methods: Whole-exome sequencing or customized gene panels were used to screen a cohort of 65 patients who had previously tested negative for all other known dystonia-associated genes., Results: We identified 14 patients (21.5%) carrying KMT2B variants, of which 1 was classified as a variant of unknown significance. We also identified 2 additional patients carrying pathogenic mutations in GNAO1 and ATM. Overall, we established a definitive genetic diagnosis in 23% of cases. We observed a spectrum of clinical manifestations in KMT2B variant carriers, ranging from generalized dystonia to short stature or intellectual disability alone, even within the same family. In 78.5% of cases, dystonia involved the lower limbs at onset, with later caudocranial generalization. Eight patients underwent pallidal DBS with a median decrease of Burke-Fahn-Marsden Dystonia Rating Scale-Motor score of 38.5% in the long term. We also report on 4 asymptomatic carriers, suggesting that some KMT2B mutations may be associated with incomplete disease penetrance., Conclusions: KMT2B mutations are frequent in childhood-onset dystonia and cause a complex neurodevelopmental syndrome, often featuring growth retardation and intellectual disability as additional phenotypic features. A dramatic and long-lasting response to DBS is characteristic of DYT-KMT2B dystonia. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)
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- 2019
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8. Lithium Treatment in Patients With Huntington's Disease and Suicidal Behavior.
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Raja M, Soleti F, and Bentivoglio AR
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- Humans, Antidepressive Agents therapeutic use, Depression drug therapy, Depression etiology, Huntington Disease complications
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- 2015
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9. Dopaminergic agents and nutritional status in Parkinson's disease.
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Laudisio A, Vetrano DL, Meloni E, Ricciardi D, Franceschi F, Bentivoglio AR, Bernabei R, and Zuccalà G
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- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Nutritional Status drug effects, Dopamine Agents adverse effects, Levodopa adverse effects, Levodopa therapeutic use, Malnutrition chemically induced, Nutritional Status physiology, Parkinson Disease drug therapy
- Abstract
Background: Malnutrition has been found in up to 24% of patients with Parkinson's disease; dopaminergic drugs might impair nutritional status. We evaluated the association of nutritional status with the use of dopaminergic agents., Methods: We analyzed data from 75 elderly patients with Parkinson's disease attending a geriatric day hospital. Nutritional status was assessed by the Mini Nutritional Assessment (MNA). Dopaminergic drugs were normalized for weight., Results: In linear regression, total levodopa (l-dopa) equivalent daily dose (LEDD) was associated with worse MNA (B = -0.14, 95% CI = -0.26--0.02; P = 0.019). This association remained significant only for l-dopa (B = -0.19, 95% CI = -0.32--0.52; P = 0.007), but not dopaminergic agent dosages. Increasing l-dopa dosages were associated with increasing probability of risk of malnutrition (P for trend = 0.049)., Conclusions: In our population, LEDD was associated with worse nutritional status and risk of malnutrition; this association was limited to use of l-dopa., (© 2014 International Parkinson and Movement Disorder Society.)
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- 2014
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10. Phenotypic variability of PINK1 expression: 12 Years' clinical follow-up of two Italian families.
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Ricciardi L, Petrucci S, Guidubaldi A, Ialongo T, Serra L, Ferraris A, Spanò B, Bozzali M, Valente EM, and Bentivoglio AR
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- Adult, Disease Progression, Female, Heterozygote, Humans, Italy, Longitudinal Studies, Male, Mental Status Schedule, Middle Aged, Phenotype, Severity of Illness Index, Family Leave, Mutation genetics, Parkinsonian Disorders genetics, Protein Kinases genetics
- Abstract
Background: Mutations in the PINK1 gene are the second most frequent cause of autosomal recessive early-onset parkinsonism., Methods: We evaluated five affected PINK1 homozygous and 14 heterozygous mutation carriers from two large Italian families over a 12-year follow-up period. Motor, nonmotor, cognitive, psychiatric, and behavioral profiles were systematically assessed. Four homozygotes and eight heterozygotes underwent magnetic resonance imaging., Results: All homozygotes showed a mild progression of motor signs and a persistent excellent response to levodopa. All but one patient complained of nonmotor symptoms and sleep impairment. Three presented impulse control disorders and two anxiety and apathy. All obtained abnormal scores at Montreal Cognitive Assessment (MoCA) and in tests sensitive to frontal functions; one presented a global cognitive impairment. Three heterozygotes showed motor signs and were diagnosed as possibly affected. They had nonmotor symptoms and cognitive impairment, and two of them showed mild bilateral temporal atrophy. Five unaffected heterozygotes reported abnormal scores at MoCA and low performances at tests sensitive to frontal functions., Conclusion: We expanded the phenotypic profile of PINK1-related parkinsonism, including psychiatric and cognitive features as part of clinical presentation., (© 2014 International Parkinson and Movement Disorder Society.)
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- 2014
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11. Alpha-synuclein repeat variants and survival in Parkinson's disease.
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Chung SJ, Biernacka JM, Armasu SM, Anderson K, Frigerio R, Aasly JO, Annesi G, Bentivoglio AR, Brighina L, Chartier-Harlin MC, Goldwurm S, Hadjigeorgiou G, Jasinska-Myga B, Jeon BS, Kim YJ, Krüger R, Lesage S, Markopoulou K, Mellick G, Morrison KE, Puschmann A, Tan EK, Crosiers D, Theuns J, Van Broeckhoven C, Wirdefeldt K, Wszolek ZK, Elbaz A, and Maraganore DM
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- Adult, Age of Onset, Aged, Aged, 80 and over, Female, Gene Frequency, Genetic Association Studies, Genotype, Humans, International Cooperation, Male, Middle Aged, Parkinson Disease mortality, Dinucleotide Repeats genetics, Genetic Predisposition to Disease genetics, Parkinson Disease genetics, Survival, alpha-Synuclein genetics
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Objectives: To determine whether α-synuclein dinucleotide repeat (REP1) genotypes are associated with survival in Parkinson's disease (PD)., Methods: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium provided REP1 genotypes and baseline and follow-up clinical data for cases. The primary outcome was time to death. Cox proportional hazards regression models were used to assess the association of REP1 genotypes with survival., Results: Twenty-one sites contributed data for 6,154 cases. There was no significant association between α-synuclein REP1 genotypes and survival in PD. However, there was a significant association between REP1 genotypes and age at onset of PD (hazard ratio: 1.06; 95% confidence interval: 1.01-1.10; P value = 0.01)., Conclusions: In our large consortium study, α-synuclein REP1 genotypes were not associated with survival in PD. Further studies of α-synuclein's role in disease progression and long-term outcomes are needed., (© 2014 International Parkinson and Movement Disorder Society.)
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- 2014
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12. Genome-wide association study in musician's dystonia: a risk variant at the arylsulfatase G locus?
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Lohmann K, Schmidt A, Schillert A, Winkler S, Albanese A, Baas F, Bentivoglio AR, Borngräber F, Brüggemann N, Defazio G, Del Sorbo F, Deuschl G, Edwards MJ, Gasser T, Gómez-Garre P, Graf J, Groen JL, Grünewald A, Hagenah J, Hemmelmann C, Jabusch HC, Kaji R, Kasten M, Kawakami H, Kostic VS, Liguori M, Mir P, Münchau A, Ricchiuti F, Schreiber S, Siegesmund K, Svetel M, Tijssen MA, Valente EM, Westenberger A, Zeuner KE, Zittel S, Altenmüller E, Ziegler A, and Klein C
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- Genetic Loci, Genetic Testing methods, Humans, Risk, Risk Factors, Arylsulfatases genetics, Dystonic Disorders genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Psychomotor Performance physiology
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Musician's dystonia (MD) affects 1% to 2% of professional musicians and frequently terminates performance careers. It is characterized by loss of voluntary motor control when playing the instrument. Little is known about genetic risk factors, although MD or writer's dystonia (WD) occurs in relatives of 20% of MD patients. We conducted a 2-stage genome-wide association study in whites. Genotypes at 557,620 single-nucleotide polymorphisms (SNPs) passed stringent quality control for 127 patients and 984 controls. Ten SNPs revealed P < 10(-5) and entered the replication phase including 116 MD patients and 125 healthy musicians. A genome-wide significant SNP (P < 5 × 10(-8) ) was also genotyped in 208 German or Dutch WD patients, 1,969 Caucasian, Spanish, and Japanese patients with other forms of focal or segmental dystonia as well as in 2,233 ethnically matched controls. Genome-wide significance with MD was observed for an intronic variant in the arylsulfatase G (ARSG) gene (rs11655081; P = 3.95 × 10(-9) ; odds ratio [OR], 4.33; 95% confidence interval [CI], 2.66-7.05). rs11655081 was also associated with WD (P = 2.78 × 10(-2) ) but not with any other focal or segmental dystonia. The allele frequency of rs11655081 varies substantially between different populations. The population stratification in our sample was modest (λ = 1.07), but the effect size may be overestimated. Using a small but homogenous patient sample, we provide data for a possible association of ARSG with MD. The variant may also contribute to the risk of WD, a form of dystonia that is often found in relatives of MD patients., (© 2013 International Parkinson and Movement Disorder Society.)
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- 2014
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13. The role of small intestinal bacterial overgrowth in Parkinson's disease.
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Fasano A, Bove F, Gabrielli M, Petracca M, Zocco MA, Ragazzoni E, Barbaro F, Piano C, Fortuna S, Tortora A, Di Giacopo R, Campanale M, Gigante G, Lauritano EC, Navarra P, Marconi S, Gasbarrini A, and Bentivoglio AR
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- Aged, Analysis of Variance, Breath Tests, Disease Eradication, Enteritis epidemiology, Enteritis prevention & control, Female, Gastric Emptying, Gastrointestinal Motility physiology, Glucose metabolism, Humans, Intestine, Small physiopathology, Male, Middle Aged, Parkinson Disease epidemiology, Parkinson Disease prevention & control, beta-Galactosidase metabolism, Enteritis complications, Helicobacter Infections complications, Helicobacter Infections epidemiology, Intestine, Small microbiology, Parkinson Disease complications
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Parkinson's disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty-three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinson's Disease Rating Scale-IV and by 1-week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half-emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed-on and no-on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%. © 2013 Movement Disorder Society., (Copyright © 2013 Movement Disorder Society.)
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- 2013
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14. Better global and cognitive functioning in choreatic versus hypokinetic-rigid Huntington's disease.
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Hart EP, Marinus J, Burgunder JM, Bentivoglio AR, Craufurd D, Reilmann R, Saft C, and Roos RA
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- Adult, Disability Evaluation, Europe, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Severity of Illness Index, Cognition Disorders diagnosis, Cognition Disorders etiology, Huntington Disease complications, Hypokinesia complications, Muscle Rigidity complications
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Background: Understanding the relation between predominantly choreatic and hypokinetic-rigid motor subtypes and cognitive and general functioning may contribute to knowledge about different motor phenotypes in Huntington's disease., Methods: In the European Huntington's Disease Network Registry study, 1882 subjects were classified as being predominantly choreatic (n=528) or hypokinetic-rigid (n=432), according to their scores on items of the total motor score a priori labeled as choreatic or hypokinetic-rigid; the other 922 patients were of a mixed type. The relationship between motor type and cognitive (verbal fluency, symbol digit modalities, Stroop color, word and interference tests) and functional (total functional capacity) capacity was investigated using multiple linear regression., Results: Motor subtype contributed significantly to the total functional capacity score (partial r(2) : 7.8%; P<.001) and to the 5 cognitive scores (partial r(2) ranged from 2.0% to 8.4%; all P<.001)., Conclusions: Patients with a predominantly choreatic motor phenotype performing better in all areas than patients with a hypokinetic-rigid motor phenotype., (Copyright © 2013 Movement Disorder Society.)
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- 2013
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15. Psychogenic facial movement disorders: clinical features and associated conditions.
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Fasano A, Valadas A, Bhatia KP, Prashanth LK, Lang AE, Munhoz RP, Morgante F, Tarsy D, Duker AP, Girlanda P, Bentivoglio AR, and Espay AJ
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- Adult, Disease Progression, Dystonia pathology, Dystonia physiopathology, Female, Functional Laterality, Humans, Male, Middle Aged, Movement Disorders complications, Retrospective Studies, Somatoform Disorders complications, Face physiopathology, Facial Injuries complications, Movement Disorders psychology, Somatoform Disorders psychology
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The facial phenotype of psychogenic movement disorders has not been fully characterized. Seven tertiary-referral movement disorders centers using a standardized data collection on a computerized database performed a retrospective chart review of psychogenic movement disorders involving the face. Patients with organic forms of facial dystonia or any medical or neurological disorder known to affect facial muscles were excluded. Sixty-one patients fulfilled the inclusion criteria for psychogenic facial movement disorders (91.8% females; age: 37.0 ± 11.3 years). Phasic or tonic muscular spasms resembling dystonia were documented in all patients most commonly involving the lips (60.7%), followed by eyelids (50.8%), perinasal region (16.4%), and forehead (9.8%). The most common pattern consisted of tonic, sustained, lateral, and/or downward protrusion of one side of the lower lip with ipsilateral jaw deviation (84.3%). Ipsi- or contralateral blepharospasm and excessive platysma contraction occurred in isolation or combined with fixed lip dystonia (60.7%). Spasms were reported as painful in 24.6% of cases. Symptom onset was abrupt in most cases (80.3%), with at least 1 precipitating psychological stress or trauma identified in 57.4%. Associated body regions involved included upper limbs (29.5%), neck (16.4%), lower limbs (16.4%), and trunk (4.9%). There were fluctuations in severity and spontaneous exacerbations and remissions (60%). Prevalent comorbidities included depression (38.0%) and tension headache (26.4%). Fixed jaw and/or lip deviation is a characteristic pattern of psychogenic facial movement disorders, occurring in isolation or in combination with other psychogenic movement disorders or other psychogenic features., (Copyright © 2012 Movement Disorder Society.)
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- 2012
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16. Age at onset and symptom spread in primary adult-onset blepharospasm and cervical dystonia.
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Martino D, Berardelli A, Abbruzzese G, Bentivoglio AR, Esposito M, Fabbrini G, Guidubaldi A, Girlanda P, Liguori R, Marinelli L, Morgante F, Santoro L, and Defazio G
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- Aged, Blepharospasm mortality, Cohort Studies, Female, Humans, Linear Models, Male, Middle Aged, Statistics, Nonparametric, Survival Analysis, Torticollis mortality, Age of Onset, Blepharospasm epidemiology, Blepharospasm physiopathology, Torticollis epidemiology, Torticollis physiopathology
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Background: The site of dystonia onset is known to affect the risk of spread in primary adult-onset focal dystonia, but other factors possibly influencing spread are unknown. This study explored the relationship between age and spread of dystonia in primary adult-onset focal dystonia., Methods: Two survival models analyzed spread of dystonia in a large cohort of patients with primary blepharospasm (BSP) and cervical dystonia. The first model was based on time interval between onset and spread of dystonia, and the second model was based on age at spread., Results: Patients presenting with BSP had a 2-fold higher rate of spread than those presenting with cervical dystonia, regardless of the survival model used. However, survival analysis, based on age at spread, showed that spread develops at a similar age period in both groups, with most spread events occurring after the age of 50., Conclusions: The convergent age of spread in BSP and cervical dystonia is a novel finding indicating age as a factor modulating spread of dystonia. These findings may assist in informing prognostication for patients with primary adult-onset focal dystonia., (Copyright © 2012 Movement Disorder Society.)
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- 2012
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17. Status dystonicus: predictors of outcome and progression patterns of underlying disease.
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Fasano A, Ricciardi L, Bentivoglio AR, Canavese C, Zorzi G, Petrovic I, Kresojevic N, Kostić VS, Svetel M, Kovacs N, Balas I, Roubertie A, Mishra D, Mariotti P, Temudo T, and Nardocci N
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- Adolescent, Adult, Age Factors, Child, Child, Preschool, Dystonic Disorders drug therapy, Dystonic Disorders etiology, Female, Humans, Male, Muscle Relaxants, Central therapeutic use, Prognosis, Sex Factors, Treatment Outcome, Disease Progression, Dystonic Disorders diagnosis
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Background: Status dystonicus (SD) is a rare, life-threatening disorder characterized by acute worsening of generalized dystonia., Methods: This study was conducted to characterize the pathogenesis, clinical course, and prognosis of SD. We reviewed the records of six centers and analyzed them together with all the cases previously reported in the literature., Results: Eighty-nine episodes occurring in 68 patients were studied. The majority of patients were males (64.7%), were <15 years of age (58.8%), and had secondary dystonia as the underlying condition (37.8%). The episodes were mainly characterized by tonic muscle spasms (68.5%), with phasic forms more common in secondary forms and among females. Almost all cases needed a multistaged approach, with surgery being the most successful strategy. Neurological conditions preceding the episode worsened in 16.2% of cases (ending in death in 10.3%)., Conclusions: The course and outcome of SD is highly variable; male gender and prevalent tonic phenotype predict a poor outcome., (Copyright © 2012 Movement Disorder Society.)
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- 2012
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18. Rivastigmine as alternative treatment for refractory REM behavior disorder in Parkinson's disease.
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Di Giacopo R, Fasano A, Quaranta D, Della Marca G, Bove F, and Bentivoglio AR
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- Aged, Cross-Over Studies, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Middle Aged, Parkinson Disease complications, Parkinson Disease drug therapy, Pilot Projects, Polysomnography, REM Sleep Behavior Disorder etiology, Rivastigmine, Cholinesterase Inhibitors therapeutic use, Phenylcarbamates therapeutic use, REM Sleep Behavior Disorder drug therapy
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Background: We report on a double-blind, crossover pilot trial for the treatment of rapid eye movement behavior disorder (RBD) in 12 patients with Parkinson's disease in whom conventional therapy failed., Methods: We employed a patch of the cholinesterase inhibitor rivastigmine at a dose of 4.6 mg/24 hours for 3 weeks compared with placebo to reduce the frequency of RBD episodes. The number of RBD episodes was monitored by diaries of bed partners., Results: Rivastigmine was well tolerated in most patients, with minor side effects, mainly related to peripheral cholinergic action, and significantly reduced the mean frequency of RBD episodes during the observation time., Conclusions: The results of this pilot trial need to be confirmed by further studies on a larger number of patients., (Copyright © 2012 Movement Disorder Society.)
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- 2012
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19. Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early-onset levodopa-responsive Parkinsonism.
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Guidubaldi A, Piano C, Santorelli FM, Silvestri G, Petracca M, Tessa A, and Bentivoglio AR
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- Adult, Antiparkinson Agents therapeutic use, Female, Genome-Wide Association Study methods, Humans, Levodopa therapeutic use, Magnetic Resonance Imaging methods, Parkinson Disease drug therapy, Parkinson Disease genetics, Mutation genetics, Parkinson Disease complications, Proteins genetics, Spastic Paraplegia, Hereditary etiology, Spastic Paraplegia, Hereditary genetics
- Abstract
Background: Autosomal recessive hereditary spastic paraplegia with thin corpus callosum is a neurodegenerative disorder characterized by spastic paraparesis, cognitive impairment, and peripheral neuropathy. The neuroradiologic hallmarks are thin corpus callosum and periventricular white matter changes. Mutations in the SPG11 gene have been identified to be a major cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and recently also proven to be responsible for juvenile parkinsonism associated with spastic paraplegia., Methods: We describe one Italian autosomal recessive hereditary spastic paraplegia with thin corpus callosum patient who unusually presented at onset, 16 years, with parkinsonism-like features, responsive to dopaminergic therapy. Then the clinical picture evolved and became more complex. A brain magnetic resonance imaging scan showed thin corpus callosum and hyperintense T(2)-weighted lesions in periventricular regions, and the (123)I-ioflupane single-photon emission coupled tomography was abnormal., Results: Genetic analysis detected two novel mutations, a c.3664insT variant in compound heterozygosity with a c.6331insG mutation, in SPG11., Discussion: This case confirms the high genetic and clinical heterogeneity associated with SPG11 mutations. It also offers further evidence that parkinsonism may initiate autosomal recessive hereditary spastic paraplegia with thin corpus callosum and that parkinsonian symptoms can have variable dopaminergic response in these patients., (Copyright © 2011 Movement Disorder Society.)
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- 2011
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20. Botulinum toxin A versus B in sialorrhea: a prospective, randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson's disease.
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Guidubaldi A, Fasano A, Ialongo T, Piano C, Pompili M, Mascianà R, Siciliani L, Sabatelli M, and Bentivoglio AR
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- Aged, Aged, 80 and over, Cross-Over Studies, Double-Blind Method, Female, Humans, Male, Middle Aged, Pilot Projects, Prospective Studies, Sialorrhea complications, Treatment Outcome, Amyotrophic Lateral Sclerosis complications, Botulinum Toxins therapeutic use, Botulinum Toxins, Type A therapeutic use, Parkinson Disease complications, Sialorrhea therapy
- Abstract
Background: Either botulinum toxins (BoNTs) A and B have been used for improving drooling in different neurological conditions., Methods: Consecutive patients affected by Amyotrophic Lateral Sclerosis (ALS) or Parkinson's Disease (PD) accompanied by severe drooling were randomized to receive botulinum neurotoxin type A (BoNT-A) or B (BoNT-B) injections into the salivary glands. Following the first treatment, when sialorrhea returned to baseline (at least three months after the first injection), subjects were re-treated with the other serotype. Ultrasound-guided injections into parotid and submandibular glands were bilaterally performed: total doses were 250 U BoNT-A (Dysport) and 2500 U BoNT-B (Neurobloc). Objective (cotton roll weight) and subjective (ad hoc clinical scales) evaluations were performed at baseline, after 1 and 4 weeks, and every 4 weeks until drooling returned to baseline., Results: Twenty-seven patients (15 ALS and 12 PD) were enrolled, fourteen completed the study. BoNT-A and BoNT-B treatments gave both subjective and objective improvements in all patients. The latency was significantly shorter after BoNT-B treatments (3.2 ± 3.7 days) compared to BoNT-A (6.6 ± 4.1 days; P = 0.002). The mean benefit duration was similar at 75 and 90 days for BoNT-A and BoNT-B, respectively (P = NS). The only toxin-related side effect was a change to saliva thickness., Conclusions: Either 250 U Dysport or 2500 U Neurobloc have similar effectiveness and safety in controlling sialorrhea. BoNT-B has a shorter latency and comparable duration. Cost analysis, considering the doses used in this study protocol favored BoNT-B treatment., (Copyright © 2010 Movement Disorder Society.)
- Published
- 2011
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21. Rare and serious cardiac side effects during ropinirole titration.
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Di Giacopo R, Fasano A, Fenici R, Loria G, and Bentivoglio AR
- Subjects
- Aged, Humans, Male, Middle Aged, Parkinson Disease drug therapy, Antiparkinson Agents adverse effects, Heart Diseases chemically induced, Indoles adverse effects
- Published
- 2010
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22. Punding in Parkinson's disease: the impact of patient's awareness on diagnosis.
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Fasano A, Pettorruso M, Ricciardi L, Conte G, and Bentivoglio AR
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- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Awareness physiology, Parkinson Disease diagnosis, Parkinson Disease physiopathology, Parkinson Disease psychology, Stereotyped Behavior physiology
- Published
- 2010
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23. Olfactory dysfunction in Parkinsonism caused by PINK1 mutations.
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Ferraris A, Ialongo T, Passali GC, Pellecchia MT, Brusa L, Laruffa M, Guidubaldi A, Paludetti G, Albanese A, Barone P, Dallapiccola B, Valente EM, and Bentivoglio AR
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Odorants, Olfaction Disorders diagnosis, Olfaction Disorders etiology, Parkinsonian Disorders complications, Sensory Thresholds physiology, Smell genetics, Young Adult, Genetic Predisposition to Disease, Olfaction Disorders genetics, Parkinsonian Disorders genetics, Protein Kinases genetics
- Abstract
Hyposmia is a common nonmotor feature of Parkinson's disease (PD) and has been variably detected in monogenic Parkinsonisms. To assess olfactory dysfunction in PINK1-related Parkinsonism, we evaluated olfactory detection threshold, odor discrimination, and odor identification in five groups of subjects: sporadic PD (n = 19), PINK1 homozygous (n = 7), and heterozygous (n = 6) parkinsonian patients, asymptomatic PINK1 heterozygous carriers (n = 12), and Italian healthy subjects (n = 67). All affected subjects and all healthy heterozygotes but one resulted hyposmic, with most patients in the range of functional anosmia or severe hyposmia. Detection threshold was more preserved and discrimination more impaired in patients with PINK1 mutations than in PD cases. Alterations of detection and discrimination were observed also in PINK1 asymptomatic heterozygotes. On the contrary, odor identification appeared to be mostly related to the disease status, as it was impaired in nearly all patients (including PD and PINK1 cases) and preserved in healthy heterozygotes. Our data indicate that olfactory dysfunction is common in PINK1 Parkinsonism and consists typically in defective odor identification and discrimination. A milder olfactory deficit, mostly involving discrimination, can be found in asymptomatic heterozygotes, possibly indicating an underlying preclinical neurodegenerative process., ((c) 2009 Movement Disorder Society.)
- Published
- 2009
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24. Mutation screening of the DYT6/THAP1 gene in Italy.
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Bonetti M, Barzaghi C, Brancati F, Ferraris A, Bellacchio E, Giovanetti A, Ialongo T, Zorzi G, Piano C, Petracca M, Albanese A, Nardocci N, Dallapiccola B, Bentivoglio AR, Garavaglia B, and Valente EM
- Subjects
- Adolescent, Adult, Age of Onset, Aged, Aged, 80 and over, Child, Child, Preschool, Cohort Studies, Female, Genetic Testing methods, Humans, Infant, Italy epidemiology, Male, Middle Aged, Young Adult, Apoptosis Regulatory Proteins genetics, DNA-Binding Proteins genetics, Dystonia Musculorum Deformans genetics, Mutation genetics, Nuclear Proteins genetics
- Abstract
Mutations in the THAP1 gene on chromosome 8p21-p22 (DYT6 locus) have been recently reported as causative of autosomal dominant primary torsion dystonia (PTD) in four Amish-Mennonite families and in 12 additional probands of different ancestry. We sequenced the THAP1 gene in 158 patients with DYT1-negative PTD who had onset of symptoms below 30 years and/or positive family history. One sporadic Greek male patient, aged 57 years, was found to carry a novel heterozygous missense variant in THAP1 exon 3 (p.Cys170Arg), of likely pathogenic significance. This subject first presented with right writer's cramp at age of 10 years and, subsequently, developed left arm dystonia and an extremely severe left laterocollis, without further spreading to other body districts. Our findings expand the genotypic spectrum of THAP1 and strengthen the association with upper body involvement, including the cranial and cervical districts that are usually spared in DYT1-PTD., ((c) 2009 Movement Disorder Society.)
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- 2009
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25. GIGYF2 variants are not associated with Parkinson's disease in Italy.
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Bonetti M, Ferraris A, Petracca M, Bentivoglio AR, Dallapiccola B, and Valente EM
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- Humans, Italy, Carrier Proteins genetics, Parkinson Disease genetics
- Published
- 2009
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26. The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease.
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Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, Bottacchi E, Cannas A, Ceravolo G, Ceravolo R, Cicarelli G, Gaglio RM, Giglia RM, Iemolo F, Manfredi M, Meco G, Nicoletti A, Pederzoli M, Petrone A, Pisani A, Pontieri FE, Quatrale R, Ramat S, Scala R, Volpe G, Zappulla S, Bentivoglio AR, Stocchi F, Trianni G, and Dotto PD
- Subjects
- Aged, Antiparkinson Agents therapeutic use, Anxiety epidemiology, Anxiety etiology, Anxiety psychology, Cognition Disorders epidemiology, Cognition Disorders etiology, Cognition Disorders psychology, Depression epidemiology, Depression etiology, Depression psychology, Fatigue epidemiology, Fatigue etiology, Fatigue psychology, Female, Gastrointestinal Diseases epidemiology, Gastrointestinal Diseases etiology, Gastrointestinal Diseases psychology, Humans, Italy epidemiology, Male, Middle Aged, Olfaction Disorders epidemiology, Olfaction Disorders etiology, Olfaction Disorders psychology, Pain epidemiology, Pain etiology, Pain psychology, Parkinson Disease complications, Parkinson Disease drug therapy, Sleep Disorders, Intrinsic epidemiology, Sleep Disorders, Intrinsic etiology, Sleep Disorders, Intrinsic psychology, Urination Disorders epidemiology, Urination Disorders etiology, Urination Disorders psychology, Parkinson Disease psychology, Quality of Life
- Abstract
We performed a multicenter survey using a semistructured interview in 1,072 consecutive patients with Parkinson's disease (PD) enrolled during 12 months in 55 Italian centers to assess the prevalence of nonmotor symptoms (NMSs), their association with cognitive impairment, and the impact on patients' quality of life (QoL). We found that 98.6% of patients with PD reported the presence of NMSs. The most common were as follows: fatigue (58%), anxiety (56%), leg pain (38%), insomnia (37%), urgency and nocturia (35%), drooling of saliva and difficulties in maintaining concentration (31%). The mean number of NMS per patient was 7.8 (range, 0-32). NMS in the psychiatric domain were the most frequent (67%). Frequency of NMS increased along with the disease duration and severity. Patients with cognitive impairment reported more frequently apathy, attention/memory deficit, and psychiatric symptoms. Apathy was the symptom associated with worse PDQ-39 score but also presence of fatigue, attention/memory, and psychiatric symptoms had a negative impact on QoL. These findings further support a key role for NMS in the clinical frame of PD and the need to address them specifically in clinical trials using dedicated scales., (2009 Movement Disorder Society.)
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- 2009
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27. Long-term effects of pallidal or subthalamic deep brain stimulation on quality of life in Parkinson's disease.
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Volkmann J, Albanese A, Kulisevsky J, Tornqvist AL, Houeto JL, Pidoux B, Bonnet AM, Mendes A, Benabid AL, Fraix V, Van Blercom N, Xie J, Obeso J, Rodriguez-Oroz MC, Guridi J, Schnitzler A, Timmermann L, Gironell AA, Molet J, Pascual-Sedano B, Rehncrona S, Moro E, Lang AC, Lozano AM, Bentivoglio AR, Scerrati M, Contarino MF, Romito L, Janssens M, and Agid Y
- Subjects
- Activities of Daily Living, Aged, Deep Brain Stimulation, Emotions physiology, Female, Humans, Longitudinal Studies, Male, Middle Aged, Neuropsychological Tests, Sickness Impact Profile, Statistics, Nonparametric, Surveys and Questionnaires, Time Factors, Globus Pallidus physiology, Parkinson Disease psychology, Parkinson Disease therapy, Quality of Life psychology, Subthalamic Nucleus physiology
- Abstract
We assessed the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) or internal pallidum (GPi-DBS) on health-related quality of life (HrQoL) in patients with advanced Parkinson's disease participating in a previously reported multicenter trial. Sickness Impact Profile (SIP) questionnaires were available for analysis in a subgroup of n = 20/20 patients with GPi-DBS and n = 45/49 patients with STN-DBS at baseline, 6 and 36 months. The SIP provides a physical dimension and a psychosocial dimension sum score and 12 category scores: Alertness/Intellectual Behavior (AIB), Ambulation (A), Body Care and Movement (BCM), Communication (C), Eating (E), Emotional Behavior (EB), Home Management (HM), Mobility (M), Recreation and Pastimes (RP), Sleep and Rest (SR), Social Interaction (SI), and Work (W). Motor functioning was assessed by means of the Unified Parkinson's Disease Rating Scale and diaries. At 6 months significant improvements in off-period motor symptoms and activities of daily living were paralleled by significant reductions in the total, physical, and psychosocial SIP score in both treatment groups. At 3 years, sustained improvements were observed in the physical dimension score, BCM, E, M, RP after STN-DBS and M, SI after GPi-DBS. All other SIP subscores approached baseline values, but were still the same or better (except C) whereas motor functioning remained stable after 36 months. STN-DBS and GPi-DBS led to significant early improvements in HrQoL. Despite sustained motor improvements many of these initial benefits were lost after 3 years. This may reflect either progression of the disease or adaptive changes in the subjective perception of health-related wellbeing over time., ((c) 2009 Movement Disorder Society.)
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- 2009
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28. Replacement of dopaminergic medication with subthalamic nucleus stimulation in Parkinson's disease: long-term observation.
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Romito LM, Contarino MF, Vanacore N, Bentivoglio AR, Scerrati M, and Albanese A
- Subjects
- Disability Evaluation, Dopamine Agents therapeutic use, Electrodes, Implanted, Female, Humans, Levodopa therapeutic use, Longitudinal Studies, Male, Motor Activity drug effects, Motor Activity physiology, Parkinson Disease physiopathology, Severity of Illness Index, Time Factors, Treatment Outcome, Deep Brain Stimulation methods, Parkinson Disease therapy, Subthalamic Nucleus physiology
- Abstract
Stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease (PD), but the medication requirements after implant are poorly known. We performed a long-term prospective evaluation of 20 patients maintained at stable dopaminergic therapy for 5 years after bilateral STN implants, who were evaluated 6 months, 1 year, 3 years, and 5 years after surgery. We measured, during the entire observation period, the effect of deep brain stimulation on motor and functional outcome measures, the levodopa equivalent daily dose and the total electrical energy delivered. At 5 years, the UPDRS motor score had improved by 54.2% and levodopa equivalent dose was reduced by 61.9%, compared with preimplant. Dopaminergic medication remained stable during the observation period, but energy was progressively increased over time. Rest tremor, rigidity, gait, lower and upper limb akinesia, and total axial score were improved in decreasing order. Postural stability and speech improved transiently, whereas on-period freezing of gait, motor fluctuations and dyskinesias recovered durably. Functional measures did not show improvement in autonomy and daily living activities after STN implant. Chronic STN stimulation allows to replace for dopaminergic medications in the long-term at the expense of an increase of the total energy delivered. This is associated with marked improvement of motor features without a matching benefit in functional measures.
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- 2009
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29. High frequency extradural motor cortex stimulation transiently improves axial symptoms in a patient with Parkinson's disease.
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Fasano A, Piano C, De Simone C, Cioni B, Di Giuda D, Zinno M, Daniele A, Meglio M, Giordano A, and Bentivoglio AR
- Subjects
- Aged, Cognition physiology, Female, Follow-Up Studies, Humans, Movement Disorders diagnostic imaging, Movement Disorders etiology, Neuropsychological Tests, Parkinson Disease complications, Parkinson Disease diagnostic imaging, Tomography, Emission-Computed, Single-Photon methods, Deep Brain Stimulation methods, Motor Cortex physiopathology, Movement Disorders therapy
- Abstract
In a primate model of Parkinson's disease (PD), the benefit of extradural motor cortex stimulation (EMCS) was associated with high-frequency stimulation (130 Hz), whereas no significant motor improvement was achieved at 10 Hz or intermediate frequencies of stimulation. We report the case of a 72-year-old female patient affected by severe PD who underwent bilateral EMCS. In baseline med-off condition the patient was unable to arise from a chair and to stand without assistance. Stimulation at 3 and 60 Hz failed to provide any improvement of symptoms, whereas, when stimulating at 130 Hz, axial akinesia and walking improved consistently: the patient, in med-off condition, was able to arise from chair and to walk without assistance. The patient underwent two brain 99mTc- Ethylcysteinate Dimer-SPECT studies: semiquantitative and Statistical Parametric Mapping revealed that the regional cerebral perfusion was significantly increased in the supplementary motor area during stimulation at 130 Hz. After five months, the benefit of EMCS gradually disappeared., ((c) 2008 Movement Disorder Society.)
- Published
- 2008
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30. GPi-DBS in Huntington's disease: results on motor function and cognition in a 72-year-old case.
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Fasano A, Mazzone P, Piano C, Quaranta D, Soleti F, and Bentivoglio AR
- Subjects
- Aged, Humans, Male, Treatment Outcome, Cognition physiology, Deep Brain Stimulation methods, Globus Pallidus physiology, Huntington Disease physiopathology, Huntington Disease therapy, Motor Activity physiology
- Abstract
Huntington's disease (HD) produces debilitating motor abnormalities that are poorly responsive to medical therapy. Deep brain stimulation (DBS) of the posteroventral globus pallidus internus (GPi) may offer a treatment option for patients with diskinetic phenotype and minimal cognitive impairment, but its role in the management of HD remains unclear and to date only two cases have been reported. We report the outcome of GPi-DBS in a 72-year-old man with HD. Stimulation at 130 Hz caused a rapid amelioration of chorea producing the worsening of bradykinesia, whereas 40 Hz stimulation (maintaining constant the total electrical energy delivered) improved chorea while preserving the ability to walk. At 1-year follow-up, chorea has completely disappeared; however, the patient was unable to stand and walk. The cognitive profile showed a progressive deterioration, with an extension of deficit from the mainly dysexecutive alterations at baseline to a more diffused cognitive deterioration., ((c) 2008 Movement Disorder Society.)
- Published
- 2008
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31. Aceruloplasminemia: a novel mutation in a family with marked phenotypic variability.
- Author
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Fasano A, Colosimo C, Miyajima H, Tonali PA, Re TJ, and Bentivoglio AR
- Subjects
- Brain metabolism, Brain pathology, Ceruloplasmin metabolism, Deferoxamine therapeutic use, Diabetes Mellitus diagnosis, Diabetes Mellitus etiology, Disease Progression, Family, Female, Heredodegenerative Disorders, Nervous System complications, Heredodegenerative Disorders, Nervous System diagnosis, Humans, Iron metabolism, Iron Chelating Agents therapeutic use, Iron Overload diagnosis, Iron Overload drug therapy, Iron Overload etiology, Magnetic Resonance Imaging, Male, Metal Metabolism, Inborn Errors complications, Metal Metabolism, Inborn Errors diagnosis, Middle Aged, Phenotype, Seizures etiology, Ceruloplasmin deficiency, Ceruloplasmin genetics, Diabetes Mellitus genetics, Heredodegenerative Disorders, Nervous System genetics, Metal Metabolism, Inborn Errors genetics, Mutation
- Abstract
Hereditary aceruloplasminemia (HA) is a rare inherited disease characterized by anemia, iron overload, diabetes, and neurodegeneration. HA is caused by the homozygous mutation of the ceruloplasmin (CP) gene. We report two siblings with markedly different phenotypes carrying a novel mutation: a homozygous deletion of two nucleotides (1257-1258 TT del) causing the premature stop of the Cp protein translation (Y401X). An early diagnosis of iron overload was made in the female sibling who was subsequently treated with deferoxamine. At the age of 54, her neurologic symptoms were limited to mild akinetic signs and a history of seizures; moreover, her fasting blood glucose level never exceeded 120 mg/dL. The male sibling, who had not received any specific treatment for HA, developed severe diabetes at the age of 32 and at 48 manifested a progressively disabling neurologic disease. Possible physiopathological bases of these intrafamilial phenotypic variations are discussed., (2008 Movement Disorder Society)
- Published
- 2008
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32. PINK1 heterozygous rare variants: prevalence, significance and phenotypic spectrum.
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Marongiu R, Ferraris A, Ialongo T, Michiorri S, Soleti F, Ferrari F, Elia AE, Ghezzi D, Albanese A, Altavista MC, Antonini A, Barone P, Brusa L, Cortelli P, Martinelli P, Pellecchia MT, Pezzoli G, Scaglione C, Stanzione P, Tinazzi M, Zecchinelli A, Zeviani M, Cassetta E, Garavaglia B, Dallapiccola B, Bentivoglio AR, and Valente EM
- Subjects
- Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Case-Control Studies, Female, Gene Frequency, Genes, Recessive, Heterozygote, Humans, Italy, Male, Middle Aged, Molecular Sequence Data, Parkinson Disease enzymology, Phenotype, Retrospective Studies, Sequence Homology, Amino Acid, Genetic Variation, Parkinson Disease genetics, Protein Kinases genetics
- Abstract
Heterozygous rare variants in the PINK1 gene, as well as in other genes causing autosomal recessive parkinsonism, have been reported both in patients and healthy controls. Their pathogenic significance is uncertain, but they have been suggested to represent risk factors to develop Parkinson disease (PD). The few large studies that assessed the frequency of PINK1 heterozygotes in cases and controls yielded controversial results, and the phenotypic spectrum is largely unknown. We retrospectively analyzed the occurrence of PINK1 heterozygous rare variants in over 1100 sporadic and familial patients of all onset ages and in 400 controls. Twenty patients and 6 controls were heterozygous, with frequencies (1.8% vs. 1.5%) not significantly different in the two groups. Clinical features of heterozygotes were indistinguishable to those of wild-type patients, with mean disease onset 10 years later than in carriers of two mutations but worse disease progression. A meta-analysis indicated that, in PINK1 heterozygotes, the PD risk is only slightly increased with a non significant odds ratio of 1.62. These findings suggest that PINK1 heterozygous rare variants play only a minor susceptibility role in the context of a multifactorial model of PD. Hence, their significance should be kept distinct from that of homozygous/compound heterozygous mutations, that cause parkinsonism inherited in a mendelian fashion., ((c) 2008 Wiley-Liss, Inc.)
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- 2008
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33. Management of status dystonicus: our experience and review of the literature.
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Mariotti P, Fasano A, Contarino MF, Della Marca G, Piastra M, Genovese O, Pulitanò S, Chiaretti A, and Bentivoglio AR
- Subjects
- Adolescent, Humans, Male, Spinal Dysraphism therapy
- Abstract
Status dystonicus (SD) is a life threatening disorder that develops in patients with both primary and secondary dystonia, characterized by acute worsening of symptoms with generalized and severe muscle contractions. To date, no information is available on the best way to treat this disorder. We review the previously described cases of SD and two new cases are reported, one of which occurring in a child with static encephalopathy, and the other one in a patient with pantothenate kinase-associated neurodegeneration. Both patients were admitted to an intensive care unit and treated with midazolam and propofol. This approach proved to be useful in the former while the progressive nature of the dystonia of the second patient required the combination of intrathecal baclofen infusion and bilateral pallidal deep brain stimulation. We believe that a rapid and aggressive approach is justified to avoid the great morbidity and mortality which characterize SD. Our experience, combined with the data available in the literature, might permit to establish the best strategies in managing this rare and severe condition., ((c) 2007 Movement Disorder Society.)
- Published
- 2007
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34. Dystonia gravidarum: a new case with a long follow-up.
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Fasano A, Elia AE, Guidubaldi A, Tonali PA, and Bentivoglio AR
- Subjects
- Adult, Female, Follow-Up Studies, Humans, Pregnancy, Pregnancy Outcome, Dystonia diagnosis, Dystonia physiopathology, Pregnancy Complications, Terminology as Topic
- Abstract
We report a case of cervical dystonia occurring in a 33-year-old without personal history of movement disorder but with family history of essential tremor, primigravid, primiparous woman at 1 weeks' amenorrhea, resolved completely after delivery in the course of 3 months. Dystonia never recurred in the following 5 years. Several neurological disorders are known to occur or worsen during pregnancy. As far as we know, this is the second reported case of dystonia occurring during pregnancy, thus confirming that dystonia gravidarum represents a new entity and should be considered in women of reproductive age affected by dystonia, especially when presenting with rapid-onset cervical dystonia., ((c) 2006 Movement Disorder Society.)
- Published
- 2007
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35. Prevalence of spinocerebellar ataxia type 2 mutation among Italian Parkinsonian patients.
- Author
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Modoni A, Contarino MF, Bentivoglio AR, Tabolacci E, Santoro M, Calcagni ML, Tonali PA, Neri G, and Silvestri G
- Subjects
- Ataxins, Family Health, Female, Humans, Italy epidemiology, Magnetic Resonance Imaging, Male, Parkinson Disease diagnostic imaging, Parkinson Disease pathology, Radionuclide Imaging, Trinucleotide Repeat Expansion genetics, Tropanes metabolism, Mutation, Nerve Tissue Proteins genetics, Parkinson Disease epidemiology, Parkinson Disease genetics
- Abstract
We evaluated the prevalence of the SCA2 mutation among 224 Italian patients affected by typical Parkinsonism, including 145 sporadic and 79 familial forms. Pink1, Parkin, and LRRK2 gene mutations had been excluded previously. Molecular testing for the CAG expansion at the SCA 2 locus was performed on leukocyte DNA. Cloning and sequencing of the expanded allele was performed in patients positive for the SCA2 expansion. A 38 CAG expansion was detected in 1 of 79 families studied. The proband, a male age 67, and his sister, age 69, were both affected by a benign form of L-dopa-responsive Parkinsonism not associated with cerebellar signs. The inheritance was autosomal dominant. The CAG expansion was stable through meiotic transmission: sequence analysis showed that the CAG stretch was interrupted by 3 CAA. Our study shows that CAG expansion at the SCA 2 locus may represent a genetic cause of familial L-dopa-responsive Parkinsonism among Italian patients. The stability of the pathological CAG expansion detected in this family was related to the presence of CAA interruptions. These findings, together with literature data, suggest that the molecular intrinsic structure of the expanded allele may modulate the phenotypic expression of the SCA2 mutation.
- Published
- 2007
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36. Non-DYT1 early-onset primary torsion dystonia: comparison with DYT1 phenotype and review of the literature.
- Author
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Fasano A, Nardocci N, Elia AE, Zorzi G, Bentivoglio AR, and Albanese A
- Subjects
- Adolescent, Adult, Age Factors, Aged, Child, Chromosome Deletion, Disability Evaluation, Disease Progression, Female, Humans, Male, Middle Aged, Neurologic Examination, Torticollis diagnosis, Torticollis genetics, Trinucleotide Repeats, Dystonia Musculorum Deformans diagnosis, Dystonia Musculorum Deformans genetics, Molecular Chaperones genetics, Phenotype
- Abstract
To investigate the clinical features of early-onset primary torsion dystonia (EO-PTD), 57 consecutive genetically characterized patients with onset before 21 years were studied. Sex, ethnic origin, family history of dystonia, age at onset, disease duration, site of dystonia onset and distribution at latest examination, dystonia progression, time to generalization, and motor disability were noted. The 14 patients (25%) with GAG deletion (904_906/907_909delGAG) in the DYT1 gene were compared with the remaining non-DYT1 patients. Cranial involvement was present in 49% of non-DYT1 cases, but only 14% of DYT1 cases; non-DYT1 patients were younger at time of generalization. DYT1 cases had features similar to sporadic non-DYT1 cases but differed markedly from familial non-DYT1 cases, the latter having later age at onset, less common limb onset, more frequent cervical involvement, and slower progression than DYT1 PTD. These findings indicate that non-DYT1 forms of EO-PTD differ clinically from those of DYT1 forms. Cranial involvement before 21 years of age is the strongest predictor of non-DYT1 status. Positive family history and cervical involvement are associated with less severe progression in non-DYT1 forms., ((c) 2006 Movement Disorder Society.)
- Published
- 2006
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37. Frequency and phenotypes of LRRK2 G2019S mutation in Italian patients with Parkinson's disease.
- Author
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Marongiu R, Ghezzi D, Ialongo T, Soleti F, Elia A, Cavone S, Albanese A, Altavista MC, Barone P, Brusa L, Cortelli P, Petrozzi L, Scaglione C, Stanzione P, Tinazzi M, Zeviani M, Dallapiccola B, Bentivoglio AR, Valente EM, and Garavaglia B
- Subjects
- Amino Acid Substitution, Female, Gene Frequency, Genetic Carrier Screening, Humans, Italy, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Male, Parkinson Disease enzymology, Phenotype, Mutation, Parkinson Disease genetics, Protein Serine-Threonine Kinases genetics
- Abstract
To evaluate the frequency of the LRRK2 G2019S mutation in Italy, we tested 1,072 probands with Parkinson's disease (PD; 822 sporadic and 250 familial): 20 patients (1.9%) carried the G2019S mutation, 11 patients (1.3%) were sporadic, and 9 (4.3%) had a positive family history. Considering only probands with autosomal dominant inheritance, the G2019S frequency raises to 5.2%. All presented a typical phenotype with variable onset and shared the common ancestral haplotype. Mutation frequency raised from 1.2% in early onset PD to 4.0% in late onset PD., ((c) 2006 Movement Disorder Society)
- Published
- 2006
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38. Punding and computer addiction in Parkinson's disease.
- Author
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Fasano A, Elia AE, Soleti F, Guidubaldi A, and Bentivoglio AR
- Subjects
- Diagnostic Techniques, Neurological, Humans, Male, Middle Aged, Stereotyped Behavior, Attitude to Computers, Cumulative Trauma Disorders physiopathology, Parkinson Disease physiopathology
- Abstract
Punding is a stereotypical behavior in which there is an intense fascination with repetitive handling and examining of mechanical objects, such as taking apart watches and radios or arranging common objects (lining up pebbles, rocks, or other small objects). This disabling condition, different from both obsessive-compulsive disorder and mania, is probably underreported. Punding is thought to be related to dopaminergic stimulation, although only a few observations of this condition in patients with Parkinson's disease (PD) under therapy has been reported. We report a man with PD who developed an unusual, severe, repetitive behavior characterized by spending most of his time on his computer; this abnormal behavior was concomitant with the introduction of L-dopa (400 mg per day) and was not associated to a pattern of chronic inappropriate overuse of dopaminergic medication or other psychiatric symptoms. The patient had the feeling he was forced into a disruptive and unproductive behavior, and he made several attempts to quit without succeeding., ((c) 2006 Movement Disorder Society)
- Published
- 2006
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39. Analysis of blink rate in patients with blepharospasm.
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Bentivoglio AR, Daniele A, Albanese A, Tonali PA, and Fasano A
- Subjects
- Humans, Reference Values, Videotape Recording, Blepharospasm physiopathology, Blinking
- Abstract
The blink rate (BR) during rest, conversation, and reading was assessed in 50 patients with blepharospasm (BS) and in 150 healthy subjects. BR at rest and during conversation was higher in patients with BS. Moreover, 76% of patients had BR higher at rest than during conversation, whereas in 74% of controls, BR was higher during conversation than at rest. The sensitivity and specificity of two parameters (value of BR at rest and pattern rest-BR higher than conversation-BR) in discriminating patients and controls were computed. The best fit was obtained with a rest-BR above 27 blinks per minute. When the two parameters were combined (rest-BR above 27 blinks per minute together with the pattern rest-BR higher than conversation-BR), we obtained a 92.3% sensitivity and a 82.0% specificity in discriminating between BS patients and controls. These findings indicate that specific features of BR can be associated with BS, suggesting that the analysis of BR might be helpful for the diagnosis of BS in early stages., ((c) 2006 Movement Disorder Society)
- Published
- 2006
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40. PINK1 mutations are associated with sporadic early-onset parkinsonism.
- Author
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Valente EM, Salvi S, Ialongo T, Marongiu R, Elia AE, Caputo V, Romito L, Albanese A, Dallapiccola B, and Bentivoglio AR
- Subjects
- Adult, Age of Onset, Aged, Female, Gene Dosage, Humans, Male, Middle Aged, Polymorphism, Genetic genetics, Mutation, Parkinsonian Disorders enzymology, Parkinsonian Disorders genetics, Protein Kinases genetics
- Abstract
We have recently reported homozygous mutations in the PINK1 gene in three consanguineous families with early-onset parkinsonism (EOP) linked to the PARK6 locus. To further evaluate the pathogenic role of PINK1 in EOP and to draw genotype-phenotype correlates, we performed PINK1 mutation analysis in a cohort of Italian EOP patients, mostly sporadic, with onset younger than 50 years of age. Seven of 100 patients carried missense mutations in PINK1. Two patients had two PINK1 mutations, whereas in five patients only one mutation was identified. Age at onset was in the fourth-fifth decade (range, 37-47 years). The clinical picture was characterized by a typical parkinsonian phenotype with asymmetric onset and rare occurrence of atypical features. Slow progression and excellent response to levodopa were observed in all subject. Two of 200 healthy control individuals also carried one heterozygous missense mutation. The identification of a higher number of patients (5%) than controls (1%) carrying a single heterozygous mutation, along with previous positron emission tomography studies demonstrating a preclinical nigrostriatal dysfunction in PARK6 carriers, supports the hypothesis that haploinsufficiency of PINK1, as well as of other EOP genes, may represent a susceptibility factor toward parkinsonism. However, the pathogenetic significance of heterozygous PINK1 mutations still remains to be clarified.
- Published
- 2004
- Full Text
- View/download PDF
41. Treatment with botulinum neurotoxin of gastrointestinal smooth muscles and sphincters spasms.
- Author
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Brisinda G, Bentivoglio AR, Maria G, and Albanese A
- Subjects
- Enteric Nervous System drug effects, Enteric Nervous System physiopathology, Humans, Muscle, Smooth drug effects, Pain drug therapy, Pain etiology, Treatment Outcome, Anti-Dyskinesia Agents therapeutic use, Botulinum Toxins therapeutic use, Gastrointestinal Diseases drug therapy, Spasm drug therapy
- Abstract
Local injections of botulinum neurotoxin are now considered an efficacious treatment for neurological and non-neurological conditions. One of the most recent achievements in the field is the observation that botulinum neurotoxin provides benefit in diseases of the gastrointestinal tract. Botulinum neurotoxin inhibits contraction of gastrointestinal smooth muscles and sphincters; it has also been shown that the neurotoxin blocks cholinergic nerve endings in the autonomic nervous system, but it does not block nonadrenergic responses mediated by nitric oxide. This aspect has further promoted the interest to use botulinum neurotoxin as a treatment for overactive smooth muscles, such as the anal sphincters to treat anal fissure and outlet-type constipation, or the lower esophageal sphincter to treat esophageal achalasia. Knowledge of the anatomical and functional organization of innervation of the gastrointestinal tract is a prerequisite to understanding many features of botulinum neurotoxin action on the gut and the effects of injections placed into specific sphincters. This review presents current data on the use of botulinum neurotoxin to treat diseases of the gastrointestinal tract and summarizes recent knowledge on the pathogenesis of disorders of the gut due to a dysfunction of the enteric nervous system., (Copyright 2004 Movement Disorder Society)
- Published
- 2004
- Full Text
- View/download PDF
42. Phenotypic characterization of DYT13 primary torsion dystonia.
- Author
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Bentivoglio AR, Ialongo T, Contarino MF, Valente EM, and Albanese A
- Subjects
- Activities of Daily Living classification, Adolescent, Adult, Aged, Child, Child, Preschool, Chromosome Mapping, Chromosomes, Human, Pair 1, Disability Evaluation, Dystonia Musculorum Deformans diagnosis, Dystonic Disorders diagnosis, Female, Follow-Up Studies, Histone Acetyltransferases, Humans, Male, Middle Aged, Neurologic Examination, Pedigree, Penetrance, Chromosome Aberrations, Dystonia Musculorum Deformans genetics, Dystonic Disorders genetics, Genes, Dominant genetics, Phenotype, TATA-Binding Protein Associated Factors genetics, Transcription Factor TFIID genetics
- Abstract
We describe the phenotype of DYT13 primary torsion dystonia (PTD) in a family first examined in 1994. A complete neurological evaluation was performed on all available family members: 8 individuals were definitely affected by dystonia. The family was re-evaluated in March 2000: at that time, 3 more individuals had developed symptoms of dystonia. Inheritance of PTD was autosomal dominant, with affected individuals spanning three consecutive generations and male-to-male transmission. Age at onset ranged from 5 to 43 years. Onset occurred either in the craniocervical region or in upper limbs. Progression was mild, and the disease course was benign in most affected individuals; generalization occurred only in 2 cases. We did not find anticipation of age at onset or of disease severity through generations. Most subjects presented with jerky, myoclonic-like dystonic movements of the neck or shoulders. DYT13-PTD is an autosomal dominant disease, with incomplete penetrance (58%). Clinical presentation and age at onset were more variable than in DYT1-PTD, and the neck was involved in most of those affected. Moreover, the individuals with generalised dystonia were not severely disabled and were able to lead independent lives. To date, this is the only family with DYT13-PTD.
- Published
- 2004
- Full Text
- View/download PDF
43. Analysis of the epsilon-sarcoglycan gene in familial and sporadic myoclonus-dystonia: evidence for genetic heterogeneity.
- Author
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Valente EM, Misbahuddin A, Brancati F, Placzek MR, Garavaglia B, Salvi S, Nemeth A, Shaw-Smith C, Nardocci N, Bentivoglio AR, Berardelli A, Eleopra R, Dallapiccola B, and Warner TT
- Subjects
- Adolescent, Adult, Aged, Cytoskeletal Proteins genetics, Female, Humans, Male, Membrane Glycoproteins genetics, Middle Aged, Pedigree, Polymerase Chain Reaction, Sampling Studies, Sarcoglycans, Syndrome, Cytoskeletal Proteins analysis, Dystonic Disorders genetics, Genetic Heterogeneity, Membrane Glycoproteins analysis, Myoclonus genetics
- Abstract
The epsilon-sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus-dystonia. Linkage to the SGCE locus has been detected in the majority of families tested, and mutations in the coding region have been found recently in families with autosomal dominant myoclonus-dystonia. To evaluate the relevance of SGCE in myoclonus-dystonia, we sequenced the entire coding region of the epsilon-sarcoglycan gene in 16 patients with either sporadic or familial myoclonus-dystonia. No mutations were found. This study suggests that epsilon-sarcoglycan does not play an important role in sporadic myoclonus-dystonia and supports genetic heterogeneity in familial cases., (Copyright 2003 Movement Disorder Society)
- Published
- 2003
- Full Text
- View/download PDF
44. Clinical and subclinical dopaminergic dysfunction in PARK6-linked parkinsonism: an 18F-dopa PET study.
- Author
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Khan NL, Valente EM, Bentivoglio AR, Wood NW, Albanese A, Brooks DJ, and Piccini P
- Subjects
- Adult, Aged, Dopamine genetics, Female, Fluorine Radioisotopes, Genetic Carrier Screening, Genetic Markers genetics, Humans, Male, Middle Aged, Parkinsonian Disorders metabolism, Pedigree, Statistics, Nonparametric, Dopamine physiology, Genetic Linkage, Parkinsonian Disorders diagnostic imaging, Parkinsonian Disorders genetics, Tomography, Emission-Computed methods
- Abstract
PARK6, a locus for early-onset recessive parkinsonism, has been causally implicated in nine unrelated families from four different countries. The gene is still unidentified and hence the importance of PARK6 as a cause of Parkinson's disease is unknown. To date, no pathology or functional imaging studies are available on PARK6-linked parkinsonism. We have used (18)F-dopa positron emission tomography to study four patients who are homozygous and three asymptomatic relatives who are heterozygous for PARK6. The clinically affected PARK6 subjects had a similar 85% reduction in posterior dorsal putamen (18)F-dopa uptake to a group of idiopathic Parkinson's disease patients matched for clinical disease severity and duration but showed significantly greater involvement of head of caudate and anterior putamen. The group of asymptomatic PARK6 carriers showed a significant mean 20 to 30% reduction in caudate and putamen (18)F-dopa uptake in comparison with controls, individual values falling toward the bottom of the normal range. Our results indicate that PARK6 pathology results in a more uniform loss of striatal dopamine terminal function than Parkinson's disease. The subclinical loss of striatal dopamine storage capacity found in the PARK6 carriers implies that the unidentified gene on the short arm of chromosome 1 exhibits either haploinsufficency or a dominant negative effect.
- Published
- 2002
- Full Text
- View/download PDF
45. Transient mania with hypersexuality after surgery for high frequency stimulation of the subthalamic nucleus in Parkinson's disease.
- Author
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Romito LM, Raja M, Daniele A, Contarino MF, Bentivoglio AR, Barbier A, Scerrati M, and Albanese A
- Subjects
- Adult, Arousal physiology, Bipolar Disorder physiopathology, Dominance, Cerebral physiology, Electrodes, Implanted, Female, Follow-Up Studies, Humans, Male, Middle Aged, Motivation, Neurologic Examination, Parkinson Disease physiopathology, Postoperative Complications physiopathology, Bipolar Disorder diagnosis, Electric Stimulation Therapy, Parkinson Disease therapy, Postoperative Complications diagnosis, Sexual Behavior physiology, Subthalamic Nucleus physiopathology
- Abstract
Among 30 Parkinson's disease patients who received high frequency stimulation of the subthalamic nucleus, 5 developed remarkable disorders of mood or sexual behavior after the implant. We describe 2 men who developed mania and hypersexuality a few days after the implant that lasted for some months and then gradually disappeared spontaneously., (Copyright 2002 Movement Disorder Society)
- Published
- 2002
- Full Text
- View/download PDF
46. Phenotypic variability of DYT1-PTD: does the clinical spectrum include psychogenic dystonia?
- Author
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Bentivoglio AR, Loi M, Valente EM, Ialongo T, Tonali P, and Albanese A
- Subjects
- Adult, Chromosomes, Human, Pair 9 genetics, Dystonic Disorders complications, Female, Genetic Variation, Humans, Male, Middle Aged, Pedigree, Phenotype, Videotape Recording, Carrier Proteins genetics, Dystonic Disorders genetics, Molecular Chaperones
- Abstract
Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous group of movement disorders, usually inherited in an autosomal dominant manner with reduced (30-40%) penetrance. The DYT1 gene on chromosome 9q34 is responsible for most cases of early limb-onset PTD. DYT1-PTD clinical spectrum is broad, as the disease may present with several degrees of body involvement and severity. We identified an Italian family with 4 members definitely affected by PTD, genetically diagnosed as carriers of the GAG mutation at DYT1 gene. Phenotype was homogeneous when considering the presentation at onset (limb involvement and early onset), the disease progression was variable; in the subjects of the last generation, the disease progressed to a severe, generalized PTD; in the remaining 2 subjects, dystonia presented with writer's cramp or upper body segmental dystonia of mild severity. One family member, carrier of the GAG mutation on DYT1 gene and mother of the most severely affected individual, presented with a clinically established psychogenic movement disorder resembling dystonia initially diagnosed as a severe generalized PTD. Psychogenic movement disorders are among the most controversial and challenging diseases to diagnose, in particular when the affected individual belongs to a family with an inherited movement disorder., (Copyright 2002 Movement Disorder Society)
- Published
- 2002
- Full Text
- View/download PDF
47. PARK6-linked parkinsonism occurs in several European families.
- Author
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Valente EM, Brancati F, Ferraris A, Graham EA, Davis MB, Breteler MM, Gasser T, Bonifati V, Bentivoglio AR, De Michele G, Dürr A, Cortelli P, Wassilowsky D, Harhangi BS, Rawal N, Caputo V, Filla A, Meco G, Oostra BA, Brice A, Albanese A, Dallapiccola B, and Wood NW
- Subjects
- Adult, Age of Onset, Antiparkinson Agents therapeutic use, Europe, Female, Founder Effect, Haplotypes, Humans, Levodopa therapeutic use, Male, Middle Aged, Parkinson Disease drug therapy, Pedigree, Phenotype, Chromosomes, Human, Pair 1, Family Health, Genetic Linkage, Parkinson Disease genetics
- Abstract
The Parkin gene on 6q25.2-27 is responsible for about 50% of autosomal recessive juvenile parkinsonism and less than 20% of sporadic early-onset cases. We recently mapped a novel locus for early-onset parkinsonism (PARK6) on chromosome 1p35-p36 in a large family from Sicily. We now confirm linkage to PARK6 in eight additional families with Parkin-negative autosomal recessive juvenile parkinsonism from four different European countries. The maximum cumulative pairwise LOD score was 5.39 for marker D1S478. Multipoint linkage analysis gave the highest cumulative LOD score of 6.29 for marker D1S478. Haplotype construction and determination of the smallest region of homozygosity in one consanguineous family has reduced the candidate interval to a 9cM region between markers D1S483 and D1S2674. No common haplotype could be detected, excluding a common founder effect. These families share some clinical features with the phenotype reported for European Parkin-positive cases, with a wide range of ages at onset (up to 68 yrs) and slow progression. However, features typical of autosomal recessive juvenile parkinsonism, including dystonia at onset and sleep benefit, were not observed in PARK6-linked families, thus making the clinical presentation of late-onset cases indistinguishable from idiopathic Parkinson's disease. PARK6 appears to be an important locus for early-onset parkinsonism in European Parkin-negative patients.
- Published
- 2002
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