Alfonso Rubino

Excessive Daytime Sleepiness in Multiple System Atrophy (SLEEMSA Study)

BACKGROUND Sleep disorders are common in multiple system atrophy (MSA), but the prevalence of excessive daytime sleepiness (EDS) is not well known. OBJECTIVE To assess the frequency and associations of EDS in MSA. DESIGN Survey of EDS in consecutive patients with MSA and comparison with patients with Parkinson disease (PD) and individuals without known neurologic disease. SETTING Twelve tertiary referral centers. PARTICIPANTS Eighty-six consecutive patients with MSA; 86 patients with PD matched for age, sex, and Hoehn and Yahr stage; and 86 healthy subject individuals matched for age and sex. MAIN OUTCOME MEASURES Epworth Sleepiness Scale (ESS), modified ESS, Sudden Onset of Sleep Scale, Tandberg Sleepiness Scale, Pittsburgh Sleep Quality Index, disease severity, dopaminergic treatment amount, and presence of restless legs syndrome. RESULTS Mean (SD) ESS scores were comparable in MSA (7.72 [5.05]) and PD (8.23 [4.62]) but were higher than in healthy subjects (4.52 [2.98]) (P < .001). Excessive daytime sleepiness (ESS score >10) was present in 28% of patients with MSA, 29% of patients with PD, and 2% of healthy subjects (P < .001). In MSA, in contrast to PD, the amount of dopaminergic treatment was not correlated with EDS. Disease severity was weakly correlated with EDS in MSA and PD. Restless legs syndrome occurred in 28% of patients with MSA, 14% of patients with PD, and 7% of healthy subjects (P < .001). Multiple regression analysis (with 95% confidence intervals obtained using nonparametric bootstrapping) showed that sleep-disordered breathing and sleep efficiency predicted EDS in MSA and amount of dopaminergic treatment and presence of restless legs syndrome in PD. CONCLUSIONS More than one-quarter of patients with MSA experience EDS, a frequency similar to that encountered in PD. In these 2 conditions, EDS seems to be associated with different causes.

Sexual dysfunction in Parkinson's disease.

Sexual dysfunction is one of the more disabling and poorly investigated aspects of PD. Several variables should be considered when evaluating sexual dysfunction in a disease in which physical, psychological, neurobiological and pharmacological features merge and are not easily distinguishable. Although sexual dysfunction is common in Parkinsons disease, the development of hypersexuality and aberrant sexual behaviour, probably due to dopamine replacement therapy, calls into question the role of dopamine in sexual behaviour. This paper reviews studies that have investigated sexual behaviour and dysfunction in PD patients, paying particular attention to the effect of dopamine replacement therapy.

Does a volume reduction of the parietal lobe contribute to freezing of gait in Parkinson's disease?

BACKGROUND Freezing of gait (FOG) is as a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk. Structural neuroimaging studies on FOG in PD using volumetric techniques yielded variable and partially conflicting findings, probably reflecting the heterogeneity and complexity of the phenomenon. The aim of this study was to further explore the differences in local gray matter (GM) volume in patients with PD with and without FOG by using Voxel-Based Morphometry (VBM). MATERIALS AND METHODS We enrolled 26 patients (7 women and 19 men) with a diagnosis of PD in stable treatment with dopaminergic therapy. Thirteen patients classified as FOG+ were matched with thirteen non-freezer (FOG-) PD patients. All 26 participants underwent a detailed neuropsychological assessment as well as a VBM analysis derived from T1 weighted 3T MRI. RESULTS The patient groups did not significantly differ for age, disease duration, H&Y stage, UPDRS part-III or educational attainment. No significant differences of cognitive profile emerged. PD-FOG+ patients showed a pattern of relative GM atrophy in left posterior parietal gyrus compared with PD-FOG-. DISCUSSION Our results suggest that a specific pattern of cortical volume reduction involving posterior parietal cortex contributes to the occurrence of FOG in PD. These data agree with the growing body of evidence considering the parietal posterior cortex as an associative area involved in spatial control of motor behavior, par-taking in response selection to sensory evaluation.

High prevalence of extrapyramidal signs and symptoms in a group of Italian dental technicians

BackgroundOccupational and chronic exposure to solvents and metals is considered a possible risk factor for Parkinsons disease and essential tremor. While manufacturing dental prostheses, dental technicians are exposed to numerous chemicals that contain toxins known to affect the central nervous system, such as solvents (which contain n-hexane in particular) and metals (which contain mercury, iron, chromium, cobalt and nickel).MethodsWe performed an epidemiological and clinical study on all 27 dental technicians working in a school for dental technicians. We asked all the technicians to fill in a self-administered questionnaire on extrapyramidal symptoms, and the General Health Questionnaire (GHQ), a self-administered screening instrument, to detect any psychiatric disorders. Moreover, we invited all 27 dental technicians to undergo a neurological examination and provide a detailed occupational history in our clinic.ResultsOf the 14 subjects who underwent the neurological examination, four had postural tremor and one had a diagnosis of Parkinsons disease.ConclusionWe found a high prevalence of extrapyramidal signs and symptoms in this group of male dental technicians working in a state technical high school in Rome. We believe that this finding may be due to the presence of toxins in the dental technicians work.

Genetic Architecture of MAPT Gene Region in Parkinson Disease Subtypes.

The microtubule-associated protein tau (MAPT) region has been conceptualized as a model of the interaction between genetics and functional disease outcomes in neurodegenerative disorders, such as Parkinson disease (PD). Indeed, haplotype-specific differences in expression and alternative splicing of MAPT transcripts affect cellular functions at different levels, increasing susceptibility to a range of neurodegenerative processes. In order to evaluate a possible link between MAPT variants, PD risk and PD motor phenotype, we analyzed the genetic architecture of MAPT in a cohort of PD patients. We observed a statistically significant association between the H1 haplotype and PD risk (79.5 vs 69.5%; χ2 = 9.9; OR, 1.7; 95% CI, 1.2–2.4; p = 0.002). The effect was more evident in non tremor dominant (TD) PD subjects (NTD-PD) (82 vs 69.5%; χ2 = 13.6; OR, 2.03; 95% CI, 1.4–3; p = 0.0003), while no difference emerged between PD subgroup of tremor dominant patients (TD-PD) and control subjects. Examination of specific intra-H1 variations showed that the H1h subhaplotype was overrepresented in NTD-PD patients compared with controls (p = 0.007; OR, 2.9; 95% CI, 1.3–6.3). Although we cannot exclude that MAPT variation may be associated with ethnicity, our results may support the hypothesis that MAPT H1 clade and a specific H1 subhaplotype influence the risk of PD and modulate the clinical expression of the disease, including motor phenotype.

DAT gene polymorphisms (rs28363170, rs393795) and levodopa-induced dyskinesias in Parkinson's disease

L-dopa-induced dyskinesias (LID) is a common motor side effect of levodopa therapy of Parkinsons disease (PD). The identified predictors may only partially account for the risk of developing LID and genetic factors may contribute to this variability. The present study is aimed to investigate whether polymorphisms in the dopamine transporter gene (DAT) are associated with the risk of developing LID. Genotyping of the 40-bp VNTR (rs28363170) and rs393795 (A/C) polymorphisms of the DAT gene was performed in a well-characterized cohort of 181 Italian PD patients in treatment with L-DOPA for 3 years or more. The results of our study show that there is no difference in dyskinesias prevalence among carriers of the two DAT gene polymorphisms. However, the combination of the two genotypes 10R/10R (rs28363170) and A carrier (rs393795) of the DAT gene reduces the risk of LID occurrence during long-term therapy with l-DOPA with respect to the PD subjects who did not carry these alleles (OR = 0.31; 95% CI, 0.09-0.88). Also based on a logistic regression analysis, the 10R/10R and the A carrier allele of the rs393795 polymorphisms of the DAT gene, could reduce the susceptibility to develop LID during levodopa therapy adjusted by demographical and clinical variables (OR = 0.19; 95% CI, 0.05-0.69). Additional studies further investigating the rs28363170 and rs393795 polymorphisms with LID in PD are needed to clarify their role in different ethnicities.