Loredana Raciti

[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.

Restless legs syndrome and multiple sclerosis: a population based case−control study in Catania, Sicily

A population‐based case−control study in the city of Catania, Sicily, was carried out to determine restless legs syndrome (RLS) prevalence and its association with multiple sclerosis (MS).

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

A possible spatial and temporal cluster of multiple sclerosis in the town of Linguaglossa, Sicily: an update.

Several cluster studies on multiple sclerosis (MS) have been reported in literature till date. The intuitive definition of a cluster of cases is an excess number of new cases of the disease within a small area and over a short period. At the end of 2000, we identified a possible cluster of MS in Linguaglossa, a little town in the province of Catania, Sicily [1]; prevalence rate on January 1, 2001, was 203/100,000 (95% CI 107–352), whereas the average annual onset-adjusted incidence risk was 18.2/100,000 (95% CI 5.9–42.5) during the last decade 1991–2000. Both prevalence and incidence were significantly higher than rates reported in Sicily and in continental Italy, [2–4]; furthermore, incidence risk was significantly higher respect to the incidence estimated in the same community during the previous decade 1981–1990 [1]. On the basis of this consideration, we hypothesized a possible spatial and temporal cluster of MS, and we now carried out a further epidemiological survey to update the incidence of MS in the community of Linguaglossa during the last quinquennium 2001–2006. Linguaglossa is located in the North-East side of the Etna volcano. Its official population in 2001, date of the last census, was 5422 inhabitants [5]; the population was quite stable during the last 20 years and can be considered ethnically stable [1]. As for the previous survey, patients with MS were primarily identified by interview with all general practitioners of the study area; archives of the Neurological Departments, MS Centers present in the province of Catania, and rosters of the local Italian Multiple Sclerosis Association were also revised. For comparison, patients with MS were defined according to the Poser’s Diagnostic criteria [6]. Background and methods have been extensively reported elsewhere [1]. Prevalence was based on the number of patients who were living in the study area on January 1, 2006, prevalence day (PD), and who had the clinical onset while living there (onset-adjusted prevalence rate). We analyzed all the sources up to January 1, 2008, to detect the patients who had the clinical onset of disease before the PD, but fulfilled the diagnostic criteria adopted after the PD. Incidence was studied from January 1, 2001, to January 1, 2006, and was based on the year of the clinical onset. During the previous survey, we identified 11 defined patients with MS who had experienced the onset of the disease before January 1, 2001 (PD). From January 1, 2001, to January 1, 2006, other six patients (one man and five women) resident in the study area had the clinical onset and the diagnosis of MS, giving an onset-adjusted prevalence of 313.5/100,000 (95% CI 164–462) and 256.3/100,000 (95% CI 219.9–305.3) age-adjusted to the Italian population (official census 2001) [5] Of the 17 prevalent patients with MS, 10 (58.8%) presented a relapsing–remitting course and seven (41.1 %) presented a secondary progressive course. None of these cases reported some kinship up to the second-degree relatives (grandparents). During the last quinquennium, January 1, 2001, to January 1, 2006, the mean annual incidence risk of MS was 22.1/100,000 (95% CI 12.7–35.9), slightly higher respect to the incidence estimated in the previous study period (18.2/100,000 in both quinquennia 1991–1995 and 1996–2001) as shown in Table 1. The average population in the community of Linguaglossa was stable during the study period (5411 inhabitants during 2001–2006 and 5491 during 1991–2001). Incidence was higher in women, 35.4 per 100,000 per year (95% CI 17.7–63.3), than in men, 7.7 per 100,000 per year (95% CI 1.8–18.0) with a female-to-male incidence ratio of 4.6. The sex ratio recorded during this last quinquennium was higher respect to the sex incidence ratio estimated during the previous decade (for both quinquennia 1991–1995 and 1996–2000 the sex ratio was 1.4). However, these findings should be interpreted with caution because of the small size of the population investigated. The mean length of time between the date of clinical onset and the date of the diagnosis was 19 ± 23 months. Both prevalence and incidence of MS have still increased in the communities of Linguaglossa during the last quinquennium investigated. Incidence risk is significantly higher than that estimated in Catania town (capital of the province) [4,5]; furthermore, MS incidence estimated during the last 15 years was also significantly higher than incidence risk recorded in Linguaglossa during the decade 1981–1990 (3.6/100,000) [1], estimate, this latter, close to that reported in Catania during the same period [4,5]. Considering that the accuracy in diagnostic procedures has not further improved over this last

Clinical diagnostic tricks for detecting psychogenic gaze paralysis

Sirs, Vertical gaze paralysis is characterized by the inability to make voluntary movements in the vertical plane leading to a loss of up and/or downward eye movements. Conjugate vertical saccade paralysis is usually related to bilateral rostral midbrain lesions. Nevertheless, several disorders of ocular motility have been frequently associated with diseases characterized by the conversion of mental distress to physical symptoms [1]. In attempt to identify these psychogenic ocular motor disorders, it could be useful during the neurological examination to attend for key signs. We describe the case of a woman presenting an upward gaze paralysis associated with peculiar clinical signs orienting through a psychogenic nature of her disorder. A 30-year-old woman was admitted in our neurological center for a referred complete upward gaze paralysis. Neuroophthalmological examination showed a bilateral esotropia of the eyes in the primary position with pupils equal in size and normally reacting to light. The examination of vertical conjugate eye movements pointed out a complete upward gaze palsy associated to convergence spasm of the right eye with miosis when asked to look up towards the examiner’s finger. During the attempted upward gaze it was observed that eyebrow elevation and frontal corrugation were absent (Fig. 1a). When horizontal ocular movements were examined, extreme lateral gaze elicited the appearance of convergence spasm mimicking right abducens palsy (Fig. 1b). Even though vestibulo-ocular reflex was normal, when repeatedly tested we occasionally noted the occurrence of convergence spasm. When the patient was distracted, binocular as well as monocular movements appeared normal in range. There was no light-near dissociation, nystagmus, any referred diplopia or ptosis. Complete ocular movements examination is reported in Video S1, S2 and S3. Neurological examination was otherwise unremarkable. Laboratory analysis, neurophysiological examination and brain magnetic resonance imaging were normal. Psycho-diagnostic assessment evidenced the presence of important affective disorder associated with marked difficulty in social relationships, affective inhibition, introversion and slowed thoughts processes. Vertical gaze paralysis commonly results from midbrain lesions, usually strokes and tumors [2]. In our patient the otherwise unexplainable vertical paralysis was associated to an identified psychiatric condition. Nevertheless, diagnosis of psychogenic movement as well as psychogenic ocular motor disorders should not be regarded as a diagnosis of exclusion, but it should be based on positive clinical signs identified by clinical examination. First of all, we noted the absence of eyebrow elevation and frontal corrugation in the attempted upward gaze, a clear indication of an impaired volition to perform the movement required. In addition, the patient frequently showed the occurrence of convergence spasm, considered one of the most common signs in psychogenic ocular motor disorders [3], also elicited by the vestibuloocular reflex. Psychogenic movement disorders occur in 2–3% of movement disorder clinic patients [4], but the prevalence of neuro-ophthalmological manifestation is not exactly known. According to the diagnostic classification of psychogenic movement disorders [5], in our case the diagnosis could be formulated as ‘clinically established’ being attributed to an underlying affective disorder. Indeed, our patient presented clinical incongruence with a classical manifestation of gaze paralysis, an abrupt onset and temporal inconsistency.

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.

Temperament Traits And Executive Functions In Parkinson's Disease.

INTRODUCTION Aim of the study was to evaluate the possible relationship between Temperament traits and executive dysfunction in patients with Parkinsons disease (PD). METHODS Patients affected by PD diagnosed according to the UK Parkinsons disease Society Brain Bank criteria were enrolled in the study. Patients with a Mini Mental State Examination <24 were excluded from the study. The Temperament and Character Inventory (TCI), a self-report questionnaire assessing the Harm Avoidance (HA), Novelty Seeking (NS) and Reward Dependence (RD) temperamental traits, has been performed. The executive functions were assessed with the Frontal Assessment Battery (FAB). RESULTS Fifty PD patients (28 men and 22 women; mean age 59.1 ± 10.1 years) were enrolled. High HA (mean score 73.3 ± 24.7) and a low NS score (24.2 ± 18.7) were recorded. Fifteen (30%) patients presented a pathological FAB score (≤13.5). Patients with a pathological FAB score presented an HA score significantly higher than patients with normal FAB score (respectively 84.9 ± 13.7 versus 69.8 ± 26.9; p = 0.045). At the univariate analysis an association between high HA score and pathological FAB score was found (OR 3.85, 95%CI 1.06-13.9; p-value 0.040). CONCLUSION Our study confirmed an association between executive disturbances and HA in PD patients, possibly related to a common impairment of the frontostriatal circuits.