Self-reported autonomic symptoms in Parkinson's disease: properties of the SCOPA-AUT scale.

BACKGROUND AND AIM: Autonomic symptoms in Parkinson's disease (PD) are very common and contribute to the severity of patient's disability. We evaluated the occurrence of autonomic symptoms in Greek patients with PD utilizing the Scales for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-AUT), a specific 23-item self-completed questionnaire for the assessment of autonomic dysfunction in patients with PD. SUBJECTS AND METHODS: One hundred and sixty-one PD patients and forty matched controls were enrolled in the study. Clinical assessment was performed with the Hoehn and Yahr scale. Patients completed a demographic questionnaire, the Non-Motor Symptoms Questionnaire (NMSQuest), the Parkinson's Disease Questionnaire (PDQ-39) and the SCOPA-AUT scale which was properly translated into Greek and validated for the study. RESULTS: SCOPA-AUT scale showed a good reliability profile and  correlated well with other measures for non-motor symptoms and health-related quality measures in PD patients. PD patients scored higher than controls in the total SCOPA -AUT score (mean score 11.9 versus 6.4). Patients reported problems in many items of the SCOPA-AUT, but the most common autonomic symptoms emerged in the Urinary and the Gastrointestinal domains. Especially sialorrhea, constipation, straining for defecation, incontinence and nocturia differentiated patients from controls. Furthermore, mean total SCOPA-AUT score correlated with duration and severity of the disease. CONCLUSION: Autonomic symptoms in PD are too important to remain undetected. By incorporating into everyday practice the use of suitable and reliable questionnaires, physicians will be able to adequately detect and manage these symptoms. Hippokratia 2016, 20(2):115-120.

Evaluation of non-motor symptoms in Parkinson's Disease: An underestimated necessity.

BACKGROUND AND AIM: Νon-motor symptoms in Parkinson's disease (PD) are very common and contribute to the severity of patient's disability. We evaluated the frequency of nonmotor symptoms in patients with PD and we explored the influence of disease characteristics on the presence of these symptoms. PATIENTS AND METHODS: One hundred sixty six patients and sixty six matched controls were enrolled in the study. The Non-Motor Symptoms Questionnaire (NMSQuest), a 30-item self-completed questionnaire, was used for the evaluation of nonmotor symptoms. RESULTS: Non-motor symptoms were more common in PD patients than controls. Mean ± SD NMSQuest score was 6.76 ± 4.22 in PD patients and 5.44 ± 4.45 in controls (p=0.035). The more common non-motor symptoms in PD patients were urinary urgency (54.3%), nocturia (51.8%), constipation (45.7%) and sadness (42.1%). There was a correlation between NMSQuest score and severity of the disease. CONCLUSION: Non-motor symptoms in PD are too important to remain undetected. By incorporating into every day practice the use of suitable, reliable questionnaires, we will be able to facilitate detection and management of these symptoms.

Sympathetic skin response in Parkinson's disease before and after mental stress.

OBJECTIVES: This study aims to evaluate sympathetic sudomotor activity in Parkinson's disease (PD) by means of the sympathetic skin response (SSR) and explore its possible changes due to mental stress. METHODS: Sudomotor function was evaluated using SSR in 29 patients with PD (Hoehn and Yahr stage I-IV) without any clinical evidence of autonomic dysfunction. Twenty-seven healthy matched controls were also evaluated. SSR was elicited by electrical stimulation of the right median nerve and simultaneously recorded on the palms of both hands. Arithmetic mental stress was evoked by means of the WAIS-R arithmetic subscale. Latency and amplitude of SSR were evaluated before and after arithmetic mental stress. RESULTS: The SSR was obtained in all patients and controls. There were no significant differences in its mean latency and amplitude between patients and controls. SSR parameters were significantly correlated with disease duration, UPDRS score, and disease stage. There were also significant correlations with rigidity and bradykinesia, but not with tremor. Mental stress had no effect on SSR parameters in any group. CONCLUSIONS: SSR parameters in PD without autonomic dysfunction were comparable to matched controls. Although PD patients are sensitive to mental stress, the arithmetic task had no effect on SSR parameters. Consequently, SSR as a method of evaluation of sympathetic sudomotor function is not sufficient for exploration of subclinical autonomic dysfunction in PD, but should be combined with other tests of autonomous nervous system.

Cerebral amyloid angiopathy.

The aim of this report was to describe the case of an elderly patient with cerebral amyloid angiopathy and associated dementia who presented with new onset symptomatology compatible with an acute cerebrovascular event. Computed tomography scanning was suggestive of an incipient ischemic cerebrovascular event. Magnetic resonance imaging was requested due to the presence of small hyperdense lesions on CT, and revealed multiple diffuse hypodense parenchymal lesions with hemosiderin deposits, indicative of cerebral amyloid angiopathy. Diagnosis of the underlying pathology is of importance, as aspirin use, and antiplatelet use in general, may in these patients be associated with microbleed burden.

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.

[Immune factors or depression? Fatigue correlates in Parkinson's disease]. / Factores inmunes o depresión? La fatiga relacionada con la enfermedad de Parkinson.

INTRODUCTION: Fatigue is a frequent symptom in Parkinson disease (PD), but its pathogenesis remains obscure. Fatigue may be influenced by depression and motor disability, but immunological factors have been also implicated. The purpose of the study was to assess fatigue in PD patients in relation to depression and various immunological factors. SUBJECTS AND METHODS: Forty PD patients and 26 normal matched controls were studied. Fatigue was assessed by the Fatigue Severity Scale (FSS). The Beck Depression Inventory (BDI) was employed for depression screening. The following immunological factors were estimated: a) T- and B-lymphocytes, T-lymphocyte subsets (helper/suppressor cells) as well as natural killer cells (NK); b) circulating levels of interleukins IL-1alpha, IL-1beta, IL-6, IL-1 receptor antagonist (IL-1Ra) and tumor necrosis factor-alpha. RESULTS: FSS mean score was higher in PD patients compared to controls (p < 0.01). Significant differences between patients and controls were found in the following immunological parameters. In PD patients: a) mean percentage of NK cells was higher, p < 0.01); b) IL-1beta levels were significantly increased (p < 0.01) and IL-1Ra levels were decreased (p < 0.001). FSS correlated significantly to BDI (p < 0.008). Circulating Il-1Ra levels correlated to fatigue severity (p < 0.01), but after exclusion of depressed PD subjects this correlation significance level dropped to p = 0.055. CONCLUSIONS: Our results indicate that fatigue is a common non motor symptom in PD. Immunological differences between PD patients and controls were observed in percentages of NK cells, IL-1beta and IL-1Ra blood levels. Fatigue correlated to depression and IL-Ra levels. However after exclusion of depressed subjects IL-1Ra levels showed only a tendency to significance, leaving depression as the principle correlate of fatigue.

¿Factores inmunes o depresión? La fatiga relacionada con la enfermedad de Parkinson / Immune factors or depression? Fatigue correlates in parkinson’s disease

La fatiga es un síntoma frecuente en la enfermedad de Parkinson (EP), pero su patogénesis permanecesin aclarar. El propósito de este estudio fue evaluar la fatiga de pacientes con EP en relación con los factores inmunológicos.Sujetos y métodos. Se estudiaron 40 pacientes con EP y 26 sujetos control. La fatiga se evaluó con la Fatigue SeverityScale (FSS). Se empleó el Beck Depression Inventory (BDI) para examinar la depresión. Como factores inmunológicos se estudiaron los linfocitos T y B, subclases de linfocitos T (helper y supressor), así como las células natural killer (NK), y los nivelessanguíneos de interleucinas IL-1alfa, IL-1beta, IL-6, el antagonista del receptor de IL-1 (IL-1Ra) y el factor de necrosis tumoral alfa. Resultados. Se encontró significación estadística (p < 0,01) entre los niveles sanguíneos de IL-1Ra y la gravedad de la fatiga, pero tras excluir los pacientes con depresión y EP, el nivel de significación disminuyó a p = 0,055. Conclusiones.Se hallaron diferencias inmunológicas en los niveles sanguíneos de pacientes con EP y sujetos control en los porcentajes de células NK, IL-1beta e IL-1Ra. La fatiga correlacionaba con la depresión y los niveles de IL-1Ra. Sin embargo, tras la exclusión de los pacientes con depresión, los niveles de IL-1Ra mostraron sólo una tendencia hacia la significación, y situarona la depresión como el principal factor correlacionado con la fatiga

Fatigue is a frequent symptom in Parkinson disease (PD), but its pathogenesis remains obscure.Fatigue may be influenced by depression and motor disability, but immunological factors have been also implicated. The purpose of the study was to assess fatigue in PD patients in relation to depression and various immunological factors.Subjects and methods. Forty PD patients and 26 normal matched controls were studied. Fatigue was assessed by the Fatigue Severity Scale (FSS). The Beck Depression Inventory (BDI) was employed for depression screening. The following immunological factors were estimated: a) T-and B-lymphocytes, T-lymphocyte subset(helper/suppressor cells) as well as natural killer cells (NK); b) circulating levels of interleukins IL-1alpha, IL-1beta, IL-6, IL-1 receptor antagonist (IL-1Ra) andtumor necrosis factor-alpha. Results. FSS mean score was higher in PD patients compared to controls (p < 0.01). Significant differences between patients and controls were found in the following immunological parameters. In PD patients: a) mean percentage of NK cells was higher, p < 0.01); b) IL-1beta levels were significantly increased (p < 0.01) and IL-1Ra levels weredecreased (p < 0.001). FSS correlated significantly to BDI (p < 0.008). Circulating Il-1Ra levels correlated to fatigue severity (p < 0.01), but after exclusion of depressed PD subjects this correlation significance level dropped to p = 0.055. Conclusions.Our results indicate that fatigue is a common non motor symptom in PD. Immunological differences between PD patients and controls were observed in percentages of NK cells, IL-1beta and IL-1Ra blood levels. Fatigue correlated to depression and IL-Ra levels. However after exclusion of depressed subjects IL-1Ra levels showed only a tendency to significance, leaving depression as the principle correlate of fatigue

The G2019S LRRK2 mutation is uncommon amongst Greek patients with sporadic Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting approximately 2% of the population >60 years of age. Although, the etiology of PD is still unknown, the genetic background of the disease has been documented. Recently, a mutation in the LRRK2 gene, G2019S, was associated with 3-41% and 1-2% of familial and sporadic PD, respectively suggesting a pivotal role of LRRK2 in PD. In this report, we examine the association of the G2019S mutation with sporadic late-onset PD, in an independent cohort of Greek patients and controls.

Auditory event-related potentials in Parkinson's disease in relation to cognitive ability.

Auditory event-related potentials were evaluated in 45 nondemented patients with mild to moderate Parkinson's disease and 40 matched normal controls. All patients were neuropsychologically assessed by means of the Raven Colored Progressive Matrices, four subtests of the Wechsler Memory Scale (Digit Span Forward, Logical Memory, Visual Memory, Associate Learning), and the Wisconsin Card-sorting Test. The P300 component of the auditory event-related potentials was significantly prolonged in the patients with Parkinson's disease. Correlations between P300 latency and neuropsychological measures showed significant associations with lower performance on the Raven Colored Progressive Matrices and the Wisconsin Card-sorting Test. Our results indicate that for patients with mild to moderate Parkinson's disease subtle changes in cognitive abilities may be reflected as P300 prolongation.

Clinical features of parkinsonian patients with the alpha-synuclein (G209A) mutation.

The motor and neuropsychological abnormalities in eight Greek patients with Parkinson's disease (PD) carrying the alpha-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.

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

The Parkinson's disease questionnaire (PDQ-39) is a well-validated British scale for the assessment of health-related quality of life (HQoL) in Parkinson's 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 Parkinson's 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) Cronbach's alpha coefficient and item-total Spearman's 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 3-7 days later in order to check test-retest reliability. The results showed the following: (1) The PDQ-39GrV demonstrated very good internal consistency (alpha 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.

Concurrent validity of the Test of Nonverbal Intelligence in Parkinson's disease patients.

The Test of Nonverbal Intelligence (TONI-2; L. Brown, R. J. Sherbenou, & S. Johnsen, 1990) and Raven's Colored Progressive Matrices (RCPM; J. C. Raven, 1965) are defined as language-free measures of cognitive ability. The purpose of the present study was to investigate the relation between the RCPM and the TONI-2 for samples of patients with Parkinson's disease (n = 75) and controls (n = 47). A regression equation was computed to evaluate the relation of the RCPM scores to the TONI-2 quotient. Regression equation results indicate that there is a significant overlapping linear variance between the two measures in both patients and controls.

Seizures as a presenting feature of late onset metachromatic leukodystrophy.

OBJECTIVES: We describe 2 patients with epilepsy as an early manifestation of late onset metachromatic leukodystrophy (MLD). METHODS AND RESULTS: The first patient presented with epileptic seizures at the age of 34 years while neurological and cognitive abnormalities appeared later. MRI findings were compatible with leukodystrophy and low levels of arylsulphatase-A activity confirmed MLD. The second patient developed epileptic seizures and behavioral disturbances at the age of 19 years. She remained stable and seizure free for 8 years. Afterwards she developed uncontrolled epileptic seizures and status epilepticus as well as neurological and cognitive impairment. Leukodystrophy was diagnosed by MRI findings and low levels of arylsulphatase-A activity were compatible with MLD. CONCLUSION: Our 2 cases postulate that epileptic seizures may be an early and prominent manifestation of late onset MLD.

Abnormality of N30 somatosensory evoked potentials in Parkinson's disease: a multidisciplinary approach.

PURPOSE OF THE STUDY: Assess the N30 component of median nerve somatosensory evoked potentials (SEPs) in patients with Parkinson's disease (PD) and correlate its parameters with the severity of the disease, general cognitive ability and regional cerebral blood flow (rCBF). PATIENTS AND METHODS: Twenty-three non-demented, non-depressed PD patients (at stage II and III of the disease) and 23 age- and education-matched normal controls were enrolled in the study. SEPs were elicited by median nerve stimulation. PD patients' cognitive ability was assessed by means of: 1) Raven's Colored Progressive Matrices (RCPM); 2) the Test of Non-Verbal Intelligence (TONI-2); and 3) the Wisconsin Card Sorting Test (WCST). The patients' rCBF was evaluated by HMPAO SPECT. RESULTS: There was no difference between SEP N30 latency in PD patients and controls (P > 0.05). The P20-N30 peak-to-peak amplitude was lower in PD patients bilaterally (P < 0.05), and the amplitude of N30-P40 was lower on the right side only (P < 0.05). A significant increase in the amplitude ratio P14-N20/P20-N30 was observed in PD patients (P < 0.05). The correlation of these findings with the clinical parameters of the disease, and notably motor signs, was not significant. Of the three neuropsychological tests only the RCPM showed a positive relation to right P20-N30 amplitude. Regression analysis between SEP parameters and rCBF showed a correlation of N30 amplitude with blood flow in parietal cortical areas, but not in frontal regions.

Wisconsin Card Sorting Test variables in relation to motor symptoms in Parkinson's disease.

The Wisconsin Card Sorting Test, a standard test for the assessment of executive function and free of a motor component, was employed for the assessment of 37 nondemented patients with idiopathic Parkinson's Disease and 37 matched normal controls. The symptoms of the patients were clinically assessed by means of the Unified Parkinson's Disease Rating Scale, which yielded scores for the cardinal symptoms of the disease as well as a total motor score. The Wisconsin Card Sorting Test was administered in all subjects in its original form (128 cards), and it was scored to yield 16 measures according to the instruction of the Wisconsin Card Sorting Test revised manual. Patients with Parkinson's Disease had significantly lower scores on the following test variables: number of trials administered, perseverative responses, percent perseverative responses, and failure to maintain set. The correlations between the last three variables and total motor score were statistically significant. Of the four cardinal symptoms of the disease, only rigidity correlated significantly with the number of perseverative responses and percent perseverative responses. These findings provide a clue that the lower performance of these patients on certain variables of the Wisconsin Card Sorting Test may be related to the process of the disease.

A longitudinal study of visuospatial discrimination in parkinsonian patients.

Visuospatial discrimination was evaluated longitudinally in 45 patients with idiopathic Parkinson's disease. 47 normal matched subjects served as controls. Visuospatial discrimination was assessed by means of a picture test with complex superimposed objects (Poppelreuter's test) at the beginning of the study as well as three years later. At initial evaluation the group with Parkinson's disease identified fewer objects than the control group and made more errors. Relations between performance on the visuospatial discrimination task and the main parameters of the disease were not statistically significant. At reevaluation, three years later on the same task, performance by the group with Parkinson's disease deteriorated. Longitudinal assessment of motor symptoms showed that disease progressed during the study period in 35 patients. Comparison of motor deterioration with performance on the visuospatial discrimination task showed no statistically significant relationship.

Deductive and inductive reasoning in Parkinson's disease patients and normal controls: review and experimental evidence.

In the present study, fifty-four subjects were tested; twenty-seven with idiopathic Parkinson's disease and twenty-seven normal controls matched in age, education, verbal ability, level of depression, sex and socio-economic status. The subjects were tested on eight tasks. Five of the tasks were the classic deductive reasoning syllogisms, modus ponens, modus tollendo tollens, affirming the consequent, denying the antecedent and three-term series problems phrased in a factual context (brief scripts). Three of the tasks were inductive reasoning, including logical inferences, metaphors and similes. All tasks were presented to subjects in a multiple choice format. The results, overall, have shown nonsignificant differences between the two groups in deductive and inductive reasoning, an ability traditionally associated with frontal lobes involvement. Of the comparisons performed between subgroups of the patients and normal controls concerning disease duration, disease onset and predominant involvement of the left and/or right hemisphere, significant differences were found between patients with earlier disease onset and normal controls and between bilaterally affected patients and normal controls, demonstrating an additive effect of lateralization to reasoning ability.