Giovanni Mostile

[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.

Metals and neurodegenerative diseases. A systematic review

ABSTRACT Neurodegenerative processes encompass a large variety of diseases with different pathological patterns and clinical presentation such as Amyotrophic Lateral Sclerosis (ALS), Alzheimer Disease (AD) and Parkinsons disease (PD). Genetic mutations have a known causative role, but the majority of cases are likely to be probably caused by a complex gene‐environment interaction. Exposure to metals has been hypothesized to increase oxidative stress in brain cells leading to cell death and neurodegeneration. Neurotoxicity of metals has been demonstrated by several in vitro and in vivo experimental studies and it is likely that each metal could be toxic through specific pathways. The possible pathogenic role of different metals has been supported by some epidemiological evidences coming from occupational and ecological studies. In order to assess the possible association between metals and neurodegenerative disorders, several case‐control studies have also been carried out evaluating the metals concentration in different biological specimens such as blood/serum/plasma, cerebrospinal fluid (CSF), nail and hair, often reporting conflicting results. This review provides an overview of our current knowledge on the possible association between metals and ALS, AD and PD as main neurodegenerative disorders. HighlightsMetals exposure may increase neuronal oxidative stress leading to neurodegeneration.Metals pathogenic role has been suggested by occupational and ecological studies.Results of case‐control studies on metals serum concentration are controversial.The association between metals and neurodegenerative disorders is still unclear.We provide an overview of the available evidences.

Lack of interaction between LRP1 and A2M polymorphisms for the risk of Alzheimer disease

Alzheimer disease (AD) has a heterogeneous aetiology, involving genetic and environmental factors. Low-density lipoprotein receptor-related protein 1 (LRP1), alpha-2-macroglobulin (A2M) and apolipoprotein E (APOE) are involved in molecular pathways leading to beta-amyloid deposition. Three polymorphic sites in these genes (APOE-epsilon 2/epsilon 3/epsilon 4, A2M-Ile/Val and LRP1-C/T) have been associated with AD, but the results were not univocal. We carried out a case-control study to investigate the association between these polymorphisms and the risk of developing AD and their possible interaction. We recruited 125 AD patients who fulfilled the diagnostic criteria proposed by NINCDS-ADRDA for probable or possible AD and 310 controls subjects. PCR was used to detect the polymorphisms. ORs and 95% CIs were estimated using logistic regression analysis. The OR for subjects carrying at least one allele Val (A2M-Val+) in their genotypes was 1.52 (95% CI 1.00-2.31; p=0.05); for subjects carrying at least one allele C (LRP1-C+), 1.58 (95% CI 1.00-2.50; p=0.05); for subjects carrying at least one allele epsilon 4 (APOE-epsilon 4+), 3.1 (95%CI 1.87-5.00; p<0.001). The coexistence of at least one allele Val (A2M-Val+) and one allele C (LRP1-C+) increased up two times the risk of AD (OR 2.32; 95% CI 1.23-4.35; p<0.009). No evidence of significant interaction has been found between the studied polymorphisms (p>0.05). In conclusion our study suggests that LRP1-C/T, A2M-Ile/Val and APOE-epsilon 2/epsilon 3/epsilon 4 polymorphisms are associated with AD.

The epidemiology of amyotrophic lateral sclerosis in the Mount Etna region: a possible pathogenic role of volcanogenic metals

Trace elements (TEs) may play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS) and volcanic degassing is the major natural source of TEs. Mount Etna, in the province of Catania, is the largest active volcano in Europe. Our aim was to assess the incidence of ALS in the province of Catania during 2005–2010 and its spatial distribution with respect to volcanic gas deposition.

Gender effect on non-motor symptoms in Parkinson's disease: are men more at risk?

INTRODUCTION Several gender differences have been reported in Parkinsons Disease (PD). We evaluated the burden of non-motor symptoms (NMS) in PD and the possible gender differences in their occurrence. METHODS The FRAGAMP study is a large multicenter case-control study. PD patients and controls underwent a face-to-face interview and a neurological examination performed by trained neurologists. Presence of NMS was investigated using a standardized questionnaire; cognitive impairment and depression were assessed using the Mini Mental State Examination and the Hamilton Depression Rating Scale respectively. RESULTS 585 PD patients (59.5% men) and 481 controls (34.9% men) were enrolled in the study. All NMS were significantly more frequent among PD patients than controls. PD women showed a significantly higher frequency of depression and urinary disturbances than parkinsonian men; a close frequency among PD women and men was recorded for hallucination, cognitive impairment and sleep disorders. Nonetheless, with respect to the control population, according to logistic regression stratified by sex and adjusted by age, PD men showed a stronger positive significant association with almost all NMS compared to women, excepting for urinary disturbances. The strongest association among PD men was recorded for cognitive impairment (adjusted OR 5.44 for men and 2.82 for women) and depression (adjusted OR 30.88 for men and 12.72 for women). CONCLUSIONS With respect to the general population, presence of NMS was stronger associated with male gender. Our data suggest that the presence of NMS among PD men is more strictly due to the neurodegenerative processes related to PD.

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.

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.

Obsessive-compulsive personality disorder in drug-naïve Parkinson's disease patients.

Dear Sirs, In a previous study [1] we evaluated the presence of personality disorders (PeDs) according to the DSM-IV in PD patients and controls reporting a significantly higher frequency of obsessive–compulsive personality disorder (OCPeD) among PD patients. We carried out the present study to evaluate the frequency of OCPeD in drug-naive newly diagnosed PD patients and in a group of age and sex frequency-matched healthy controls. Drug-naive PD patients [2] were enrolled from the Movement Disorders Center of the University of Catania. Controls were recruited from 10 randomly selected general practitioners rosters in the Province of Catania. The study was approved by the local ethical committee and all the subjects signed the informed consent. Clinical evaluation was made using the unified Parkinson’s disease rating scale-motor examination section (UPDRS-ME) [3]. To exclude subjects with cognitive impairment and/or DSMIV axis I disorders, the mini mental state examination (MMSE) [4] and the structured clinical interview for DSMIV axis I (SCID I) [5] were administered. To diagnose the presence of PeDs, we adopted the structured clinical interview for DSM-IV personality disorders (SCID-II) and the associated SCID-II personality questionnaire (SCID-IIPQ) [6]. The diagnosis of PeD was confirmed by a psychiatrist who was blinded respect to the diagnosis of PD even if we cannot exclude that the presence of some motor features (i.e. tremor) could have reveled the presence of the disease. To confirm the psychiatric diagnosis, all the subjects with OCPeD have been re-evaluated by a second psychiatrist blinded regarding the first evaluation. Forty drug-naive PD patients (18 men, mean age 61.5 ± 10 years) and 40 controls (20 men, mean age 57.4 ± 10.4 years) were enrolled in the study. Age and sex distributions were not significantly different between cases and controls. The mean age at disease onset among PD patients was 59.5 ± 10.7 years with a mean disease duration of 1.7 ± 1.4 years. The UPDRS-ME mean score was 23 ± 10. OCPeD was the most common PeD diagnosed among 22 PD patients (55.0 %; 95 % CI 39.6–70.4) and 7 controls (17.5 %; 95 % CI 5.7–29.3) with an OR of 5.76 (95 % CI 2.06–16.07). The second most common PeD was the DPeD recorded among 8 (20 %; 95 % CI 0–16.41) PD patients and 4 controls (10 %, 95 % CI 0–10.07) with an OR of 2.25 (95 % CI 0.62–8.18) (Table 1). Among PD patients both OCPeD and DPeD were not significantly associated with age, sex and disease duration. Frequency of OCPeD among control subjects (17.7 %) is higher than frequency on average found in the general population, even if prevalence up to 22 % has been reported [7]. This higher frequency could be probably due to random variation related to the small sample and low number of events as suggested by the width of the 95 % CI. OCPeD is defined as a pervasive pattern of preoccupation with orderliness, perfectionism, and mental and interpersonal control at the expense of flexibility, openness, and efficiency, characteristics that overlap with the wellAlessandra Nicoletti and Antonina Luca have equally contributed to this work.

Sacsin-Related Spastic Ataxia Caused by a Novel Missense Mutation p.Arg272His in a Patient from Sicily, Southern Italy

IntroductionAutosomal recessive spastic ataxia of Charlevoix-Saguenay(ARSACS) is a neurodegenerative disorder characterized byearly-onsetspasticataxia,dysarthria,nystagmus,distalmusclewasting, peripheral neuropathy, finger and foot deformities,andhypermyelinationofretinalnervefibers[1].Brainimagingoften reveals cerebellar hemispheres and superior vermis atro-phy,spinal cordatrophy, and linearhypointensitiesofthepons[2].Thegene SACS responsible fortheARSACSwasmappedto chromosome 13q11 [3] and consists in one gigantic andeight smaller upstream exons [4]. We report a novel SACSmutation in a Sicilian family with ARSACS phenotype.MethodsClinical StudyA woman, aged 36 years, was referred to our hospital forevaluation of ataxia. She was born from non-consanguineousparentsandearlymotormilestoneswerenormal.Elevenmem-bers of the family were studied. Informed consent wasobtained from all family members involved.Molecular StudyGenomic DNA of the patient and relatives was extractedfrom blood lymphocytes using standard procedure. We per-formed sequence analysis of the transcript of the SACS gene(NM_014363.4) that comprises nine exons. The nine codingexons, including the gigantic exon described previously, aswell as flanking intronic sequences of the SACS gene werepolymerase chain reaction (PCR)-amplified from genomicDNA by using 37 primer pairs. Primer sequences and am-plificationparameters are available onrequest. Purified PCRproducts (Wizard SV Gel and PCR Clean-Up System,Promega Corporation 2800 Woods Hollow Road Madison,WI 53711-5399 USA) were directly sequenced on anABI3130 automated sequencer (Applied Biosystems, FosterCity, CA, USA). In addition, mutation analysis was per-formed in patient’s parents and siblings to confirm the