Young-onset Parkinson's Disease Research Articles

ID 16 – Impulse control disorders in young-onset patients with Parkinson’s disease: Cross-sectional study seeking associated factors with regard of personal characteristics

Introduction The aim of cross-sectional study was to describe the frequency and associated factors of ICD in young-onset PD patients in specialized movement disorders centres in the Czech Republic (Prague, Brno and Olomouc). Subjects and methods 49 young-onset PD patients and 38 control subjects were examined. ICD were detected using South Oaks Gambling Screen and modified Minnesota Impulse Disorders Interview. Results Higher frequency of pathological gambling and hypersexuality was found in PD patients. Symptoms of any ICD were more frequent in patient group (13 patients (26.5%) / 4 controls (10.5%); n.s.). Higher occurrence of pathological gambling was observed in young-onset PD patients using dopamine agonists and also in subjects with dyskinesias lasting 5 years or more. Occurrence of any ICD was associated with drinking a coffee, anxiety and higher score in the domain “somatization” of psychopathology screening questionnaire (The Symptom Checklist 90). ICDs were also related to personal characteristics of patients (using Personality Style and Disorder Inventory); there was higher score in a scale of style self-confident/dissocial and aloof/schizoid. Conclusion ICDs have to be considered as a real problem in young-onset PD patients; knowledge of associated factors may be helpful in proactive seeking for these pathological types of behaviour.

Genetic and Clinical Predictors of Deep Brain Stimulation in Young-Onset Parkinson's Disease.

In a cohort of patients with young-onset Parkinson's disease (PD), the authors assessed (1) the prevalence of genetic mutations in those who enrolled in deep brain stimulation (DBS) programs compared with those who did not enroll DBS programs and (2) specific genetic and clinical predictors of DBS enrollment. Subjects were participants from 3 sites (Columbia University, Rush University, and the University of Pennsylvania) in the Consortium on Risk for Early Onset Parkinson's Disease (CORE-PD) who had an age at onset < 51 years. The analyses presented here focus on glucocerebrosidase (GBA), leucine-rich repeat kinase 2 (LRRK2), and parkin (PRKN) mutation carriers. Mutation carrier status, demographic data, and disease characteristics in individuals who did and did not enroll in DBS were analyzed. The association between mutation status and DBS placement was assessed in logistic regression models. Patients who had PD with either GBA, LRRK2, or PRKN mutations were more common in the DBS group (n = 99) compared with the non-DBS group (n = 684; 26.5% vs. 16.8%, respectively; P = 0.02). In a multivariate logistic regression model, GBA mutation status (odds ratio, 2.1; 95% confidence interval, 1.0-4.3; P = 0.05) was associated with DBS surgery enrollment. However, when dyskinesia was included in the multivariate logistic regression model, dyskinesia had a strong association with DBS placement (odds ratio, 3.8; 95% confidence interval, 1.9-7.3; P < 0.0001), whereas the association between GBA mutation status and DBS placement did not persist (P = 0.25). DBS populations are enriched with genetic mutation carriers. The effect of genetic mutation carriers on DBS outcomes warrants further exploration.

DOPA-sparing strategy in the treatment of young onset Parkinson's disease.

Context:Late onset Parkinson's disease (LOPD) is a neurodegenerative disorder afflicting individuals of ages 60 and older. However, 5–10% of cases can begin earlier between the ages 20 to 40, and are classified as young onset Parkinson disease (YOPD).Aim:In turn, this study aims to observe the trend in the choice of drug administered to patients with both YOPD and LOPD, with particular emphasis on this trend in its relation to the practice background of the neurologist.Settings and Design:A cross-sectional study was conducted in a community based Parkinson's disease and movement disorder clinic.Statistical Analysis Used:Using a retrospective chart review data was obtained and analysed.Results:The results showed that 83% of general neurologists prescribed levodopa to their patients with YOPD, whereas movement-disorder specialists took a different approach altogether. They opted not to use levodopa and, in its stead, prescribed a mixture of alternate drugs.

PARKIN Inactivation Links Parkinson's Disease to Melanoma.

Melanoma incidence is higher in patients affected by Parkinson's disease (PD) and vice versa, but the genetic link shared by both diseases is unknown. As PARK2 is both a tumor suppressor gene and frequently mutated in young onset PD, we evaluated the role of PARK2 in melanoma predisposition and progression. An in-depth PARK2 gene dosage analysis and sequencing was performed on 512 French case patients and 562 healthy control patients, as well as sporadic tumors and melanoma cell lines. The frequency of genetic alterations was compared between case patients and control patients using two-sided Fisher's exact tests and odds ratio (OR) calculations. We used western blotting to determine PARKIN expression in melanocytes and melanoma cell lines and transfection followed by clonogenic assays to evaluate the effect of PARKIN expression on cellular proliferation. All statistical tests were two-sided. Germline PARK2 mutations (including copy number variations, splicing, and putative deleterious missense mutations) were present in 25 case patients but only four control patients (OR = 3.95, 95% confidence interval = 1.34 to 15.75). Copy number variations (CNVs) and loss of heterozygosity were present in 60% and 74%, respectively, of primary tumors. PARKIN protein was expressed in melanocytes but not in most melanoma cell lines, and its expression decreased following melanocyte transformation by oncogenic NRAS. Re-expression of PARKIN in melanoma cell lines resulted in a drastic reduction of cell proliferation and inhibition of PARKIN in melanocytes stimulated their proliferation. Our results show an important role for PARK2 as a tumor suppressor both in melanoma predisposition and progression, which could explain the epidemiological association of these diseases.

Novel compound heterozygous mutations of PLA2G6 in a Korean pedigree of young-onset Parkinson's disease: A study of whole genome sequencing

Novel compound heterozygous mutations of PLA2G6 in a Korean pedigree of young-onset Parkinson's disease: A study of whole genome sequencing

Motor and cognitive deterioration in advanced young-onset PD: A cautionary tale

Motor and cognitive deterioration in advanced young-onset PD: A cautionary tale

Quality of sleep in young onset Parkinson's disease: Any difference from older onset Parkinson's disease?

Background: Sleep disorders occur commonly in Parkinson's disease and are often under-recognized and under treated in clinical practice. Objectives: To determine the quality of sleep in patients with Young onset Parkinson's disease (YOPD) and to note whether there is any difference in quality of sleep from those patients with older onset Parkinson's disease (OOPD). Methods: One hundred and fifty six patients with Parkinson's disease (YOPD-51, OOPD-105) were clinically examined and quality of sleep was determined using Pittsburgh sleep quality index (PSQI), Parkinson's disease Sleep Scale (PDSS) and Epworth Sleep Scale (ESS). Other scales included Unified Parkinson's Disease Rating Scale -part III (UPDRS-III), Hoehn & Yahr Stage, Mini Mental Status Examination, Hamilton anxiety rating scale and Hamilton depression rating scale. Results: The frequency of insomnia was higher in OOPD (55.2%) as compared to YOPD (27.5%) group (p1⁄4 0.001). The frequency of nightmareswas lower in YOPD (7.8%) when compared to OOPD (24.8%) group (p1⁄4 0.012). The mean hours of actual sleep per night were higher in YOPD patients. Global PSQI score was better in YOPD indicating good overall sleep quality in YOPD patients. The total ESS score was significantly lower in YOPD (p 1⁄4 0.019). The total PDSS score was significantly better in YOPD patients (p 1⁄4 0.018). Conclusions: Patients with YOPD had an overall better quality of sleep with lesser incidence of insomnia, nightmares, daytime sleepiness and restlessness during sleep. © 2015 Elsevier Ltd. All rights reserved.

Olfaction in Parkin single and compound heterozygotes in a cohort of young onset Parkinson's disease patients.

Parkin related Parkinson's disease (PD) is differentiated from idiopathic PD by absent or sparse Lewy bodies, and preserved olfaction. The significance of single Parkin mutations in the pathogenesis of PD is debated. To assess olfaction results according to Parkin mutation status. To compare the prevalence of Parkin single heterozygous mutations in patients diagnosed with PD to the rate in healthy controls in order to establish whether these single mutations could be a risk factor for developing PD. Parkin gene mutation testing was performed in young onset PD (diagnosed <50 years old) to identify three groups: Parkin homozygous or compound heterozygote mutation carriers, Parkin single heterozygote mutation carriers, and non-carriers of Parkin mutations. Olfaction was tested using the 40-item British version of the University of Pennsylvania smell identification test (UPSIT). Of 344 young onset PD cases tested, 8 (2.3%) were Parkin compound heterozygotes and 13 (3.8%) were Parkin single heterozygotes. Olfaction results were available in 282 cases (eight compound heterozygotes, nine single heterozygotes, and 265 non-carriers). In Parkin compound heterozygotes, the median UPSIT score was 33, interquartile range (IQR) 28.5-36.5, which was significantly better than in single Parkin heterozygotes (median 19, IQR 18-28) and non-carriers (median score 22, IQR 16-28) (ANOVA P < 0.001). These differences persisted after adjusting for age, disease duration, gender, and smoking (P < 0.001). There was no significant difference in UPSIT scores between single heterozygotes and non-carriers (P = 0.90). Patients with Parkin compound heterozygous mutations have relatively preserved olfaction compared to Parkin single heterozygotes and non-carriers. The prevalence of Parkin single heterozygosity is similar to the 3.7% rate reported in healthy controls.

Tracking Parkinson's: Study Design and Baseline Patient Data.

Background:There is wide variation in the phenotypic expression of Parkinson’s disease (PD), which is driven by both genetic and epidemiological influences.Objectives:To define and explain variation in the clinical phenotype of PD, in relation to genotypic variation.Methods:Tracking Parkinson’s is a multicentre prospective longitudinal epidemiologic and biomarker study of PD. Patients attending specialist clinics in the United Kingdom with recent onset (<3.5 years) and young onset (diagnosed <50 years of age) PD were enrolled. Motor, non-motor and quality of life assessments were performed using validated scales. Cases are followed up 6 monthly up to 4.5 years for recent onset PD, and up to 1 year for young onset PD. We present here baseline clinical data from this large and demographically representative cohort.Results:2247 PD cases were recruited (1987 recent onset, 260 young onset). Recent onset cases had a mean (standard deviation, SD) age of 67.6 years (9.3) at study entry, 65.7% males, with disease duration 1.3 years (0.9), MDS-UPDRS 3 scores 22.9 (12.3), LEDD 295 mg/day (211) and PDQ-8 score 5.9 (4.8). Young onset cases were 53.5 years old (7.8) at study entry, 66.9% male, with disease duration 10.2 years (6.7), MDS-UPDRS 3 scores 27.4 (15.3), LEDD 926 mg/day (567) and PDQ-8 score 11.6 (6.1).Conclusions:We have established a large clinical PD cohort, consisting of young onset and recent onset cases, which is designed to evaluate variation in clinical expression, in relation to genetic influences, and which offers a platform for future imaging and biomarker research.

Mutational analysis of SYNJ1 gene (PARK20) in Parkinson's disease in a Taiwanese population

Whole-exome sequencing recently identified a homozygous truncating mutation in Synaptojanin 1 (SYNJ1, PARK20), p.Arg258Gln, in 2 independent families with autosomal recessive young-onset parkinsonism with seizures and cognitive decline. This mutation's role in typical Parkinson's disease (PD) is unclear. We sequenced all coding exons and exon-intron boundaries of SYNJ1 gene in a total of 700 participants: 250 early-onset PD patients, 100 familial PD patients with family history, and 350 age/sex-matched controls from Taiwan. No patients harbored homozygous or compound heterozygous mutations of SYNJ1 gene in our study population. We observed 1 novel missense substitution, p.Ala551Val, in a single heterozygous state in 1 early-onset PD patient. This variant was not observed in controls with total 700 normal alleles. The clinical phenotype of this genetic variant carrier is similar to that seen in idiopathic PD, with motor fluctuation after 11 years of PD diagnosis and comorbidity with dementia after 13 years of motor symptoms. Our results suggest that mutations in SYNJ1 gene do not play a major role in early-onset or familial PD in our population.

PND59 - Impact of Young-onset Parkinson’s Disease on Quality of Life €“ a Literature Review

About 5-10% of the total Parkinson’s population are diagnosed from the ages of 21-45 and thus characterized as having Young-Onset Parkinson’s Disease (YOPD). Since YOPD is diagnosed during the most productive years of a patient’s life, the disease can potentially have a larger impact on quality of life (QoL), in part due to the unique psychosocial issues younger patients face. The goal of the review is to (i) identify QoL instruments utilized in YOPD and (ii) describe the studies that have utilized these instruments. A systematic literature search based on PRISMA guidelines was conducted from 2004 to 2014 using electronic databases such as Pubmed, Medline, Cochrane, and Ovid. QoL instruments validated in the general population as well as those validated in Parkinson’s Disease (PD) were included in this review. The search was limited to studies using the English language. Studies conducted exclusively on PD patients diagnosed after age 50 and review studies, were excluded. A total of 10 QoL instruments were identified (5 disease-specific, 1 condition-specific, and 4 generic). PD-specific instruments included the Parkinson’s Disease Questionnaire-39 and the Parkinson’s Impact Scale. Although frequently utilized in YOPD patients, all instruments were validated in either regular-onset PD patients (initial diagnosis greater than 45 years of age) or the general population. The literary search did not yield any YOPD-specific QoL instruments. Different experiences, emotions, and psychological issues exist between YOPD and regular-onset PD. Yet, QoL instruments validated in PD were commonly utilized in YOPD. Thus, there is a need to create YOPD-specific QoL instruments to capture the impact of this condition on young patients. In addition, the development of new YOPD-specific instruments may allow clinicians the opportunity to better understand the complexity of problems in YOPD patients to guide appropriate care of their unique condition.

Quality of sleep in young onset Parkinson's disease: Any difference from older onset Parkinson's disease.

Sleep disorders occur commonly in Parkinson's disease and are often under-recognized and under treated in clinical practice. To determine the quality of sleep in patients with Young onset Parkinson's disease (YOPD) and to note whether there is any difference in quality of sleep from those patients with older onset Parkinson's disease (OOPD). One hundred and fifty six patients with Parkinson's disease (YOPD-51, OOPD-105) were clinically examined and quality of sleep was determined using Pittsburgh sleep quality index (PSQI), Parkinson's disease Sleep Scale (PDSS) and Epworth Sleep Scale (ESS). Other scales included Unified Parkinson's Disease Rating Scale -part III (UPDRS-III), Hoehn & Yahr Stage, Mini Mental Status Examination, Hamilton anxiety rating scale and Hamilton depression rating scale. The frequency of insomnia was higher in OOPD (55.2%) as compared to YOPD (27.5%) group (p = 0.001). The frequency of nightmares was lower in YOPD (7.8%) when compared to OOPD (24.8%) group (p = 0.012). The mean hours of actual sleep per night were higher in YOPD patients. Global PSQI score was better in YOPD indicating good overall sleep quality in YOPD patients. The total ESS score was significantly lower in YOPD (p = 0.019). The total PDSS score was significantly better in YOPD patients (p = 0.018). Patients with YOPD had an overall better quality of sleep with lesser incidence of insomnia, nightmares, daytime sleepiness and restlessness during sleep.

High frequency of beta-propeller protein-associated neurodegeneration (BPAN) among patients with intellectual disability and young-onset parkinsonism

Neurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous disorder, characterized by the accumulation of iron in regions such as the basal ganglia. We enrolled 28 patients with childhood intellectual disability and young-onset parkinsonism (≤40 years at onset) and 4 patients with infantile neuroaxonal dystrophy. All had been clinically diagnosed, and the prevalence of genetic mutations linked to NBIA (PANK2 [exons 1–7], PLA2G6 [exons 2–17], C19orf12 [exons 1–3], WDR45 [exons 2–11], COASY [exons 1–9], FA2H [exons 1–7], and RAB39B [exons 1, 2]) was evaluated. We detected 7 female patients (25.0%, 7 of 28) with de novo heterozygote WDR45 mutations, which are known to be pathogenic for beta-propeller protein-associated neurodegeneration. All 7 patients had common clinical features. Pathogenic mutations in other NBIA genes were not found. We also screened 98 patients with early-onset parkinsonism without intellectual disability and 110 normal controls of Japanese origin for WDR45 mutations. None had WDR45 mutations. Our data suggest a high frequency of beta-propeller protein-associated neurodegeneration mutations in the Japanese population.

Isolated and combined dystonia syndromes - an update on new genes and their phenotypes.

Recent consensus on the definition, phenomenology and classification of dystonia centres around phenomenology and guides our diagnostic approach for the heterogeneous group of dystonias. Current terminology classifies conditions where dystonia is the sole motor feature (apart from tremor) as 'isolated dystonia', while 'combined dystonia' refers to dystonias with other accompanying movement disorders. This review highlights recent advances in the genetics of some isolated and combined dystonic syndromes. Some genes, such as ANO3, GNAL and CIZ1, have been discovered for isolated dystonia, but they are probably not a common cause of classic cervical dystonia. Conversely, the phenotype associated with TUBB4A mutations expanded from that of isolated dystonia to a syndrome of hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). Similarly, ATP1A3 mutations cause a wide phenotypic spectrum ranging from rapid-onset dystonia-parkinsonism to alternating hemiplegia of childhood. Other entities entailing dystonia-parkinsonism include dopamine transporter deficiency syndrome (SLC63 mutations); dopa-responsive dystonias; young-onset parkinsonism (PARKIN, PINK1 and DJ-1 mutations); PRKRA mutations; and X-linked TAF1 mutations, which rarely can also manifest in women. Clinical and genetic heterogeneity also characterizes myoclonus-dystonia, which includes not only the classical phenotype associated with epsilon-sarcoglycan mutations but rarely also presentation of ANO3 gene mutations, TITF1 gene mutations typically underlying benign hereditary chorea, and some dopamine synthesis pathway conditions due to GCH1 and TH mutations. Thus, new genes are being recognized for isolated dystonia, and the phenotype of known genes is broadening and now involves different combined dystonia syndromes.

A Peruvian family with a novel PARK2 mutation: Clinical and pathological characteristics.

Mutations in PARK2 result in autosomal recessive young onset Parkinson's disease (YOPD). Although there have been a number of reports on the clinical characteristics of PARK2-related PD, there is limited information available on the associated neuropathologic changes. We describe the clinical and pathological characteristics of a Peruvian family with YOPD. The proband and one unaffected sibling were screened for PARK2 dosage and point mutations. One affected sibling had detailed neuropathologic examination. Instituto Nacional de Ciencias Neurologicas (INCN) in Lima, Peru. The proband and two of her four siblings developed YOPD and both parents were unaffected. The clinical course has been characterized by akinetic-rigid parkinsonism predominantly affecting the lower limbs and dyskinesias. Analysis of PARK2 showed that the proband is compound heterozygous for a novel acceptor splice site mutation in intron 5 (IVS5-1G>A) and an exon 7 deletion. Neuropathologic assessment of an affected sibling revealed severe neuronal loss in the substantia nigra (SN) and loss of tyrosine hydroxylase immunopositive fibers in the striatum. No Lewy body pathology was observed using standard histology or immunohistochemistry for α-synuclein. Consistent with most neuropathologic reports of patients with PARK2 mutations, we did not observe Lewy body inclusions, despite marked SN degeneration and severe dopaminergic denervation of the striatum. These data describe a novel splice site mutation and further extend the clinicopathological characterization of PARK2-associated PD.

Predicting cognitive decline in Parkinson's disease: can we ask the genes?

Parkinson’s disease dementia (PDD) is characterized by progressive cognitive decline, mainly affecting executive functions, which occurs in PD patients at least 1 year after the onset of motor symptoms, when no other causes of dementia can be detected. Such temporal cut-off allows to discriminate between PDD and Lewy body disease (LBD) in which dementia is present since the disease onset, along with parkinsonism, visual hallucinations, and fluctuations in the level of consciousness. The prevalence of dementia in patients with PD is 25%, increasing up to 80% in patients with late onset after 20 years of follow-up. In contrast, PDD has been detected in only 20% of young onset PD patients after a follow-up of more than 18 years (1). Clinical criteria for probable PDD require a diagnosis of PD (2) and a slowly progressive dementia syndrome. Typical cognitive deficits in two of four domains (attention, executive function, visuospatial function, and free recall) and at least one behavioral symptom (apathy, depression/anxious mood, hallucinations, delusions, or excessive daytime sleepiness) must be present. Exclusion criteria include unknown time interval between motor and cognitive symptoms, acute confusion, resulting from systemic diseases or drug intoxication and features compatible with vascular dementia (3). In recent years, several studies have focused on predictive markers of cognitive decline in PD. Clinical, neuroimaging, and molecular markers have been identified. Nonetheless, which markers are most reliable and applicable to clinical practice to predict the long-term prognosis of these patients still needs to be clarified.

Lack of C9orf72 Repeat Expansion in Taiwanese Patients with Mixed Neurodegenerative Disorders

Background: The hexanucleotide repeat expansion in intron 1 of the C9orf72 gene is recognized as the most common genetic cause of frontotemporal dementia (FTD). There are overlapping clinical and pathological characteristics between FTD and Parkinsonism syndrome, and some FTD patients may present with Parkinsonism. The aim of this study was to analyze the hexanucleotide repeat numbers of C9orf72 gene in a mixed Taiwanese cohort with FTD, Parkinsonism syndrome, Parkinson’s disease (PD), and Alzheimer’s dementia (AD).Method: The number of hexanucleotide repeats was estimated in a total of 482 patients with mixed neurodegenerative disorders and 485 control subjects, using a two-step repeat-primed polymerase chain reaction-based genotyping strategy. The individual groups of patients included patients with Parkinsonism syndrome (n = 95), familial PD (n = 109), young-onset PD (n = 201), FTD (n = 9), sporadic AD (n = 61), and early-onset AD (n = 7).Results: We did not identify any pathogenic repeats (>30 repeats) of C9orf72 in either the patients or control subjects. However, we found one young-onset PD patient and one control subject that each had an intermediate number of repeats (25 and 21 repeats, respectively). The clinical phenotype of the young-onset PD in this patient was similar to typical idiopathic PD without additional features, and the patient responded well to levodopa treatment.Conclusion: The repeat expansion in C9orf72 is not a common cause of PD, Parkinsonism syndrome, or dementia in our population. Further studies are needed to investigate the clinical and biological significance of intermediate repeats in C9orf72.

Rapid eye movement sleep behaviour disorder in young- and older-onset Parkinson disease: a questionnaire-based study

BackgroundRapid eye movement sleep behavior disorder (RBD) is common in Parkinson disease (PD). ObjectivesTo determine the frequency of clinically probable RBD (cpRBD) in young-onset (21 to ⩽40years; YOPD) and older-onset PD (>40years; OOPD) and characterize its pattern. MethodsA total of 156 patients with PD (YOPD-51, OOPD-105) were clinically examined and the presence of RBD was diagnosed using the minimal criteria for diagnosis of RBD (International Classification of Sleep Disorders, ICSD-1). RBD screening questionnaire based on the minimal criteria was used. The bed-partners were also interviewed with Mayo sleep questionnaire. Other scales included Unified Parkinson Disease Rating Scale part III (UPDRS III), Hoehn & Yahr stage, Mini Mental Status Examination, Pittsburgh Sleep Quality Index, Parkinson Disease Sleep Scale, Epworth Sleep Scale, Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale. ResultscpRBD was diagnosed in 30 (19.2%) patients, majority being OOPD rather than YOPD (86.7% vs 13.3%; P=0.01). The frequency of RBD was significantly higher (P=0.016) in OOPD (24.8%) compared to those with YOPD (7.8%). Most often (72.4%) RBD occurred after the onset of parkinsonian symptoms. RBD was independently associated with higher global PSQI scores, total ESS scores and total PDSS scores after adjusting for the effects of age, gender, Hoehn & Yahr stage and duration of illness. ConclusionsPatients with RBD were older with later-onset motor symptoms, a more advanced stage, poorer sleep quality, and more frequent daytime sleepiness. Older-onset PD had a higher frequency of RBD than young-onset PD.

Comparing clinical features of young onset, middle onset and late onset Parkinson's disease

BackgroundParkinson's disease (PD) affects 1–2% of the population over 65 years. There is evidence that the clinical features differ with age at symptom onset, but published information is scarce. MethodsWe reviewed the charts of 593 PD patients and divided them into young onset (≤49 years), middle onset (50–69 years) and late onset (≥70 years) groups. Data collected included age at symptom onset, year of onset, family history of Parkinson's disease in first and second degree relatives, predominant first symptom, first anti parkinsonian medication prescribed, frequency of levodopa-induced dyskinesia, therapy related dystonia, therapy related gastrointestinal side effects, hallucination, dementia, depression and apathy. ResultsThe middle onset was the largest group (51%), followed by the late onset (39%) and the young onset (10%) groups. Young onset patients had a more frequent family history of Parkinson's disease and a longer survival. Symptoms other than tremor were more frequent as the initial symptom of the young onset group, and the frequency of tremor as the first symptom increased with advancing age at onset. Depression was more frequent in the young onset group. The frequency of treatment related dyskinesia or dystonia decreased with advancing age at onset. ConclusionWe have identified specific clinical differences in Parkinson's disease related to the patient's age at onset and added to the existing knowledge of the variability of disease presentation. We suggest an age of onset of 49 years or less for the definition of young onset PD.

TEN YEARS OF NEUROGENETIC REQUESTS: TO TEST OR NOT TO TEST?

BackgroundClinical neurology has benefitted significantly from advances in molecular genetics with the discovery of disease–associated genes leading to the clinical application of genetic testing. With an ever increasing arsenal of...