Donatella Contrafatto

Epilepsy and toxocariasis: a case–control study in Italy

Purpose: To assess the relationship between epilepsy and toxocariasis in adult subjects by means of a case–control study in Catania, Italy.

Non-motor symptoms: Identification and management

Non-motor symptoms are an important part of Parkinsons disease (PD) symptoms complex. They cause a significant burden on the quality of life of patients and their carers and remain a major cause of hospitalisation. Treatment of non-motor symptoms can be challenging as these symptoms are often unresponsive to conventional dopaminergic therapy. However, awareness that these symptoms are related to PD is vital as research into treatment and causation will be the cornerstone for delivering a comprehensive modern treatment for PD.

[123I]FP‐CIT‐SPECT asymmetry index to differentiate Parkinson’s disease from vascular parkinsonism

Contrafatto D, Mostile G, Nicoletti A, Dibilio V, Raciti L, Lanzafame S, Luca A, Distefano A, Zappia M. [123I]FP‐CIT‐SPECT asymmetry index to differentiate Parkinson’s disease from vascular parkinsonism.
Acta Neurol Scand: 2012: 126: 12–16.
© 2011 John Wiley & Sons A/S.

Obsessive Compulsive Personality Disorder and Parkinson’s Disease

Objectives To evaluate the frequency of personality disorders in Parkinson’s disease (PD) patients and in a group of healthy controls. Methods Patients affected by PD diagnosed according to the United Kingdom Parkinson’s disease Society Brain Bank diagnostic criteria and a group of healthy controls were enrolled in the study. PD patients with cognitive impairment were excluded from the study. Structured Clinical Interview for Personality Disorders-II (SCID-II) has been performed to evaluate the presence of personality disorders. Presence of personality disorders, diagnosed according to the DSM-IV, was confirmed by a psychiatric interview. Clinical and pharmacological data were also recorded using a standardized questionnaire. Results 100 PD patients (57 men; mean age 59.0±10.2 years) and 100 healthy subjects (52 men; mean age 58.1±11.4 years) were enrolled in the study. The most common personality disorder was the obsessive-compulsive personality disorder diagnosed in 40 PD patients and in 10 controls subjects (p-value<0.0001) followed by the depressive personality disorder recorded in 14 PD patients and 4 control subjects (p-value 0.02). Obsessive-compulsive personality disorder was also found in 8 out of 16 de novo PD patients with a short disease duration. Conclusion PD patients presented a high frequency of obsessive-compulsive personality disorder that does not seem to be related with both disease duration and dopaminergic therapy.

Presenilin-2 gene mutation presenting as Lewy Body dementia?

Presenilin-2 (PSEN2) gene mutations are a rare cause of familial and sporadic Alzheimer disease (AD) (data available on website, http://molgen-www.uia.ac.be/ADmutations). However, a Lewy Body-like dementia (DLB) phenotype has been also recently described [1]. Here, we report the case of a man presenting as DLB due to a PSEN2 mutation, which has been previously described as pathogenetic for AD [2]. A 59-year-old man, without past medical or familial history for neurological diseases, insidiously developed gait disturbance and motor impairment on the left side. After few months he presented fluctuating attentional deficits, visual hallucinations and sleep disorders characterized by vivid dreams, psychomotor agitation and somniloquio followed by progressive memory loss. The patient was treated with levodopa therapy (500 mg/day) and dopaminoagonists (pergolide 0.50 mg/day) without clinical benefits. The neurological exanimation showed extrapyramidal signs characterized by slight left arm rest tremor, bilateral upper limb postural tremor and bradykinesia on the left side. The neuropsychological examination showed significant impairment of attention (Multiple Features Targets Cancellation 1 hit 20 false alarms) [3], verbal (Rey’s Immediate Recall 25.7 n.v. C28.53; Rey’s Delayed Recall 2.2 n.v. C4.69) [4] and visuo-spatial memory (Rey’s Complex Figure Recall 1.2 n.v. C9.46) [5] as well as executive functions (Wisconsin Card Sorting Test 1/6, Frontal Assessment Battery 9.3 n.v. C13.4) [6, 7] and constructional apraxia (Rey’s Complex Figure Copy 4.5 n.v. C28.87) [5]. The Mini-Mental State Examination score was 24 and the Clinical Dementia Rating score was 1. An EEG revealed theta slow waves and sporadic middle amplitude bi-triphasic slow waves on posterior regions. Autonomic function test revealed absence of sympathetic skin response and an impaired chronotropic response during postural change and deep breathing. Chemical cerebrospinal fluid examination was normal as well as baseline blood investigations, including levels of vitamin B12, folic acid and thyroid function. The brain MRI showed an initial pattern of cerebro-vasculopathic chronic disease (hyperintensity in periventricular white matter on T2 sequences). According to McKeith criteria [8] a diagnosis of probable DLB was done. Blood sample was taken and DNA was isolated according to standard procedures. All coding and 50 noncoding exons of the PSEN1, PSEN2 [2] and APP genes (exons 16 and 17) [9] were analyzed with polymerase chain reaction amplification (PCR) and then analyzed by denaturing high performance liquid chromatography (DHPLC, Transgenomic Inc.). Pathogenetic mutations in the PSEN1 or APP gene were not found. Concerning analysis in exons 3/12 of the PSEN2 gene, the DHPLC analysis showed variant amplicon profiles of exon 4. Direct sequencing of PCR product identified the presence of a missense mutation 1839G to A at the codon 62 of exon 4, predicting the aminoacid substitution Arg62His (R62H). DNAs from relatives (two sisters, respectively 57 and 60 years old, and L. Raciti A. Nicoletti F. Le Pira D. Contrafatto S. Lanzafame T. Maci M. Zappia (&) Department of Neurosciences, University of Catania, Catania, Italy e-mail: m.zappia@unict.it

Wine drinking and essential tremor: a possible protective role.

The purpose of this study was to evaluate the possible association of cigarette smoking, coffee drinking, and wine consumption with essential tremor using a matched case–control design. Cases and controls were enrolled from 6 Movement Disorder centers in central‐southern Italy. Essential tremor was diagnosed according to Bains criteria. Three unrelated healthy controls (not affected by neurological disorders) per each enrolled case, matched by sex and age (±5 years), were selected. A standardized questionnaire was administered to record demographic, epidemiological, and clinical data. All cases and controls underwent a standard neurological examination. Adjusted odds ratios and 95% confidence intervals were estimated using conditional logistic regression for the matched cases and controls. Eighty‐three patients with essential tremor (38 men and 45 women; mean age, 68.2 ± 8.6 years) and 245 matched control subjects (113 men and 132 women; mean age, 68.4 ± 9.7 years) were enrolled in the study. Multivariate analysis showed a significant negative association between essential tremor and wine consumption preceding the onset of disease (adjusted odds ratio, 0.23; 95% confidence interval, 0.08–0.64; P = .0005) with a significant dose effect (1–2 glass of wine per day: odds ratio, 0.32; 95% confidence interval, 0.10–0.95; P = .04; more than 3 glass of wine per day: odds ratio, 0.14; 95% confidence interval, 0.03–0.62; P = .01). In our sample no association between essential tremor and cigarette smoking or coffee drinking was found. Our data suggest a negative association between wine drinking and essential tremor, which could be explained by the long‐term neuroprotective effect of its antioxidant components.

Electroencephalographic lateralization, clinical correlates and pharmacological response in untreated Parkinson's disease

BACKGROUND In Parkinsons disease (PD), different topographically defined cortical-subcortical oscillatory networks have been implicated in motor program dysfunction. Few studies have focused on clinical correlates of cortical activity asymmetry using quantitative electroencephalography. METHODS We retrospectively selected N = 34 L-dopa naïve PD subjects who had undergone standardized electroencephalography. We selected N = 18 subjects group-matched by age, sex and hand dominance with normal electroencephalography and no parkinsonism and/or cognitive decline as controls. A Welchs periodogram was applied to electroencephalographic signal epochs recorded from homologous pairs of electrodes over each hemisphere. An index of lateralization was then obtained as the absolute value of the electroencephalographic asymmetry index, computed by subtracting left from right-sided log power spectral density for each homologous site and frequency band. A standardized L-dopa acute challenge test was performed on all PD subjects to compute short-duration response magnitude. RESULTS In mid/lateral frontal regions higher index of lateralization for the beta band (p = 0.015) and lower index of lateralization for the theta band (p = 0.036) were found in PD subjects as compared to controls. Both parameters correlated with Hoehn-Yahr staging (beta: r = 0.428, p = 0.012; theta: r = -0.464, p = 0.006). In occipital region lower index of lateralization for the alpha band was found in PD correlating with L-dopa short-duration response magnitude (r = 0.456; p = 0.007). CONCLUSIONS Lateralization of frontal cortex beta electroencephalographic activity is associated with clinical disability. Occipital cortex alpha activity may relate to L-dopa responsiveness in untreated PD subjects.

Side effects induced by the acute levodopa challenge in Parkinson's Disease and atypical parkinsonisms.

Introduction Acute levodopa challenge may be performed to predict levodopa chronic responsiveness. The aim of the study was to investigate frequency of side effects during the acute levodopa challenge in PD and atypical parkinsonisms. Methods We enrolled 34 de novo PD patients and 29 patients affected by atypical parkinsonisms (Multiple System Atrophy, MSA, n = 10; Progressive Supranuclear Palsy, PSP, n = 12 and Corticobasal Degeneration, CBD, n = 7) who underwent an acute levodopa challenge. Side effects occurring during test were recorded. Results Side effects were more frequent among atypical parkinsonisms as unique group when compared to PD patients (64.3% versus 23.5%; p-value 0.002) with an adjusted OR of 4.36 (95%CI 1.40–13.5). Each atypical parkinsonisms showed almost double occurrence of side effects (MSA 90%, PSP 41.7% and CBD 57%). Conclusions Side effects during acute levodopa challenge may be frequent in atypical parkinsonisms. This information could be useful in order to better prepare the patient for the test. Furthermore, it could represent a useful cue in differential diagnosis with PD.

Switching L-dopa Therapy from Pulsatile to Pulse Administration Reduces Motor Complications in Parkinsonʼs Disease

Objective To evaluate the severity of wearing-off and dyskinesia in patients with complicated Parkinson disease (PD) after switching L-dopa oral therapy from a “pulsatile” administration, consisting in intermittent multiple daily small doses of the drug, to a “pulse” administration, consisting in standard oral doses given at specific interdose intervals. Methods Thirty-four PD patients with motor complications were monitored twice with standardized waking day motor status evaluations using the Unified Parkinson Disease Rating Scale-Motor Examination (UPDRS-ME) and the Abnormal Involuntary Movement Scale (AIMS) after switching L-dopa administration modality from “pulsatile” to “pulse.” To quantify predictable motor fluctuations, a Wearing Off Index was computed based on changes in treatment response magnitude. Results On the whole, after switching from “pulsatile” to “pulse” administration, there was a reduction in number of L-dopa daily doses and an increase in the amount of the dosage of the single doses, AIMS maximum score decreased without increasing motor disability. More specifically, in predominant fluctuating patients, there was a significant reduction in UPDRS-ME average score as well as in Wearing Off Index. In predominant dyskinetic patients, there was a significant reduction in average and maximum AIMS scores with no changes in average and maximum UPDRS-ME scores. Conclusions Switching L-dopa therapy from “pulsatile” to “pulse” modality may reduce the severity of wearing-off and dyskinesia in complicated PD.

Dopaminergic and non-dopaminergic gait components assessed by instrumented timed up and go test in Parkinson’s disease

The timed up and go test (TUG) is a widely used clinical test for the evaluation of balance and mobility. An instrumented version of TUG (iTUG) has been proposed to provide quantitative information on TUG performances. Here, we hypothesized that l-dopa may differently influence gait parameters recorded by a portable inertial sensor. To test this idea, we evaluated iTUG test in patients with Parkinson’s disease (PD), both in l-dopa OFF and ON state. Twenty-eight PD patients performed the iTUG. Subjects were instructed to perform the task both in practical “OFF” and “ON” state. The system differentiated the test in six phases, recording phase durations, three-axial accelerations, average and peak angular speeds during turning. In all patients, sit-to-stand vertical and medio-lateral accelerations together with turning phase duration and angular speeds improved after l-dopa administration, while sit-to-stand and stand-to-sit phases antero-posterior accelerations were less responsive. In PD, l-dopa modulates iTUG in different ways, mostly improving the turning phases and less acting on postural controls during the sit-to-stand and stand-to-sit phases. Our results suggest different involvement of dopaminergic mechanisms on gait as assessed by iTUG. This is important for those aspects which are not improved by pharmacological therapy.