Sevasti Bostantjopoulou

Clinical features of parkinsonian patients with the α-synuclein (G209A) mutation†

The motor and neuropsychological abnormalities in eight Greek patients with Parkinsons disease (PD) carrying the α‐synuclein gene mutation (G209A) were studied. These patients (five men, three women) belonged to six different families. Their symptoms started between 32–50 years of age (mean ± SD, 39.7 ± 7.6 years) and they had a mean disease duration of 5.4 ± 2.1 years (range, 2–9 years) at the time of examination. Rigidity and bradykinesia predominated both at disease onset as well as in the later stages and rest tremor was relatively uncommon. Neuropsychological assessment showed that one patient was mildly demented while another had impairment in memory, visuoconstructive abilities, and executive function. Depression was present in only one patient. Our findings indicate that genetic forms of parkinsonism share common motor and cognitive characteristics with sporadic PD but raise the possibility that greater cognitive impairment and the relative rarity of tremor may be distinctive features worthy of further investigation.

Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Greece

Mutations in beta-glucocerebrosidase gene (GBA) have been implicated in Parkinson disease (PD). A Greek cohort of 172 PD patients and 132 control individuals were screened for GBA mutations by complete sequencing of the genes exons. Four mutations previously associated with Gaucher disease and/or Parkinsons disease (L445P, D409H, E326K, H255Q) were detected, as well as five newly identified variants (R329H, L268L, S271G, T428K, V460L), providing for the first time data regarding the frequency of GBA mutations among PD patients and controls, in the Greek population. H255Q was the most common GBA mutation among Greek PD patients (4/172). V460L was only found in control individuals (2/132). Overall, GBA mutations were significantly overrepresented in a subgroup of early onset PD patients, compared to controls (P = 0.019, OR = 4.2; 95%CI = 1.28 -- 13.82), suggesting that GBA mutations may modify age of onset for PD.

The genetic background of Parkinson's disease: current progress and future prospects.

Almost two decades of genetic research in Parkinsons disease (PD) have remarkably increased our knowledge regarding the genetic basis of PD with numerous genes and genetic loci having been found to cause familial PD or affect the risk for PD. Approximately 5–10% of PD patients have monogenic forms of the disease, exhibiting a classical Mendelian type of inheritance, however, the majority PD cases are sporadic, probably caused by a combination of genetic and environmental risk factors. Nowadays, six genes, alpha synuclein, LRRK2, VPS35, Parkin, PINK1 and DJ‐1, have definitely been associated with an autosomal dominant or recessive PD mode of inheritance. The advent of genome‐wide association studies (GWAS) and the implementation of new technologies, like next generation sequencing (NGS) and exome sequencing has undoubtedly greatly aided the identification on novel risk variants for sporadic PD. In this review, we will summarize the current progress and future prospects in the field of PD genetics.

Pharmacological treatment and the prospect of pharmacogenetics in Parkinson's disease.

Parkinson disease (PD) is a progressive movement disorder marked by tremor, rigidity, bradykinesia and postural instability. Levodopa (l‐dopa), usually combined with a peripheral dopa decarboxylase inhibitor, has been proved to provide the best symptomatic benefit for PD. However, its long‐term efficacy is limited because of motor complications and drug‐induced dyskinesia. Dopamine agonists, catechol‐O‐methyltransferase inhibitors and monoamine oxidase‐B inhibitors are anti‐parkinsonian (anti‐PD) drugs that have been found to further improve the potency of l‐dopa and prevent the onset of motor complications. However, as PD is a progressive disorder, all the drugs used for its therapy, manifest reduced efficacy and adverse effects with time. Research on the field of pharmacogenetics has pointed out that the genetic variability of each individual determines to a large extent the inter‐individual variability in response to anti‐PD drugs. Clinicogenetic trials show that drug efficacy or toxicity or susceptibility to side effects are features governed by genetic principles. This article is a review of the present pharmacological treatment of PD and current pharmacogenetic data for PD.

Assessing quality of life in Parkinson's disease: Can a short‐form questionnaire be useful?

Various instruments with good psychometric properties have been developed for the assessment of health‐related quality of life (HRQoL) in Parkinsons disease, (PD); however, in everyday practice a brief questionnaire is needed for quick screening of patients. We present the process of development and validation of the Greek version of PD questionnaire‐8 (PDQ‐8GrV), which is an 8‐item scale derived from a well‐known measure for the evaluation of HRQoL in PD, the PD questionnaire (PDQ‐39). PDQ‐8 GrV was applied to 228 nondemented Greek PD patients. Data from PDQ‐39 were also collected from these patients for comparisons between the total scores of the two scales. Detailed statistical analysis showed that PD‐8GrV has psychometric properties analogous to its parent questionnaire.

Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

Objectives To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinsons Disease. Methods A retrospective study of genetic Parkinsons diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. The right:left asymmetry index and striatal asymmetry index was calculated. Results Scans were available from 37 cases of monogenetic Parkinsons disease (7 glucocerebrosidase (GBA) mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin). The asymmetry of radioligand uptake for Parkinsons disease with GBA or LRRK2 mutations was greater than that for Parkinsons disease with alpha synuclein, PINK1 or Parkin mutations. Conclusions The asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss.

Quality of life in Parkinson's disease: Greek translation and validation of the Parkinson's disease questionnaire (PDQ-39)

The Parkinsons disease questionnaire (PDQ-39) is a well-validated British scale for the assessment of health-related quality of life (HQoL) in Parkinsons disease (PD). The PDQ-39 has been translated into Greek and it was applied to 119 Greek PD patients. These patients were classified in stages according to the Hoehn and Yahr (HY) scale and their motor disability was assessed by means of the Unified Parkinsons disease rating scale (UPDRS) as well as the Schwab and England activities of daily living scale (ADL). The Beck depression inventory (BDI) was applied for the evaluation of depression. The translated version of PDQ-39, designated PDQ-39GrV, was validated as follows: (1) Cronbachs α coefficient and item — total Spearmans rank — order correlations were calculated in order to estimate the internal consistency of PDQ-39GrV scales. (2) Validity of the PDQ-39GrV was examined in terms of agreement with the clinical assessment parameters (stage, UPDRS, ADL and BDI scores). (3) Sixty one PD patients were re-evaluated 3–7days later in order to check test-retest reliability. The results showed the following: (1) The PDQ-39GrV demonstrated very good internal consistency (α: 0.71–0.94). Item — total correlations were statistically significant (r: 0.52–0.93). Test-retest measurements correlated significantly (p = 0.001). (2) Clinically obtained motor parameters correlated well with PDQ-39GrV scales influenced by physical aspects of the disease, while emotionally and socially influenced ones correlated with depression. Our findings indicate that PDQ-39 GrV is a reliable, easy to administer scale for the assessment of HQoL in Greek PD patients.

Pupil Light Reflex in Parkinson's Disease: Evaluation With Pupillometry

ABSTRACT We evaluated pupil light reflex (PLR) in patients with Parkinsons disease (PD) and normal controls by means of pupillometry and explored its possible relation to clinical characteristics in parkinsonian patients. PLR was evaluated using pupillometry in 66 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited by single flash stimuli of 24.6 candelas/m2 intensity and 20 ms duration, and six parameters were studied after full recording of pupils movement. A significant increase in latency (T1) and significant decrease in amplitude (R1–R2), maximum constriction velocity (Vmax), as well as maximum acceleration (ACmax) was found in parkinsonian patients. There was no significant difference in initial radius (R1) and minimum radius (R2) values. Of the parameters studied, ACmax emerged as a significant predictor for discrimination between PD patients and controls. There was no significant correlation between pupillometry parameters and clinical characteristic of patients (disease duration, stage, and the Unified Parkinsons Disease Rating motor scale). The study demonstrates PLR disorder in PD patients even without overt clinical autonomic dysfunction. Pupillometry appears to be a useful and noninvasive method for exploration of PLR alterations in PD and may prove to be useful for the early detection of subclinical autonomic nervous system dysfunction.

Association of the Tau haplotype with Parkinson's disease in the Greek population.

We compared the distribution of the Tau H1 haplotype and related subhaplotypes in a group of clinically diagnosed Parkinsons disease patients (n = 133) and in control individuals (n = 113) from northern Greece. We were able to detect a statistically significant overrepresentation of the H1H1 genotype in our patient group (OR for H1H1 vs. H1H2 and H2H2: 1.73; 95% CI: 1.03–2.90; P = 0.037). The H1 subhaplotype significantly associated with the disease in our population was different from the one previously reported for a Norwegian population, suggesting that the nature of the association of Tau with Parkinsons disease is influenced by ethnic variation.

Motor and Nonmotor Features of Carriers of the p.A53T Alpha-Synuclein Mutation: A Longitudinal Study

G209A SNCA mutation carriers represent an important group of genetic PD. We describe motor and nonmotor features of G209A SNCA mutation carriers.