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Sleep disturbances are common in patients with Parkinson's disease (PD). We aimed to evaluate prevalence and severity of nighttime sleep disturbances in Italian PD patients and to validate the Italian version of the Parkinson's disease sleep scale. A total of 221 PD patients and 57 healthy controls participated in a cross-sectional study with retest. PDSS, Epworth Sleepiness Scale (ESS), Hamilton Depression Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehn and Yahr staging were applied. PDSS total and individual items scores from patients were significantly lower than those in controls. Internal consistency of PDSS scale was satisfactory and intraclass correlation coefficient for test-retest reliability was 0.96 for total PDSS score. A significant negative correlation was found between total PDSS and ESS scores, and between total PDSS and HDRS scores. PDSS scores were also related to UPDRS sections II, III and IV, and H&Y stage. PDSS and ESS scores were not related to levodopa equivalent dose. Daytime sleepiness, depressive symptoms and disease severity correlate with sleep disturbances in Italian PD patients. The PDSS is a valid and reliable tool to evaluate sleep disturbances in Italian patients.

OBJECTIVE: To characterize brain metabolic changes associated with mild cognitive impairment (MCI) in drug-naive patients with Parkinson disease (PD) using (18)F-fluorodeoxyglucose (FDG) and PET (FDG-PET). METHODS: This cross-sectional study included newly diagnosed patients with PD with MCI in single or multiple domain (PD-MCI; n =12) and without MCI (PD-nMCI; n =12), and healthy controls (n =12). The groups were matched for age. Moreover, the patient groups were matched for motor disability. All subjects underwent a FDG-PET study. Cerebral regional relative metabolic maps were compared in PD-MCI, PD-nMCI, and controls using regions of interest analysis (ROIs) and voxel-based analysis with statistical parametric mapping. RESULTS: ROIs and voxel-based analyses revealed significant relative hypometabolism in the prefrontal, superior/inferior parietal, and associative occipital cortices as well as in the striatum in patients with PD-MCI relative to controls (p < 0.05) and to a lesser extent in patients with PD-nMCI. In contrast, patients with PD-nMCI did not show significant metabolic changes as compared to controls. CONCLUSION: MCI in patients with PD is associated with cortical hypometabolism since the earliest stage, independent of therapy or motor disability. The early involvement of posterior cortical region, a pattern shared by advanced stages of PD-MCI and PD with dementia, could represent an early marker of dementia. The relevance of this pattern in predicting prodromal dementia has to be evaluated in longitudinal studies.

Objectives—To determine the occurrence of celiac disease in a population of ataxic patients without definite diagnosis and to characterise distinctive features which may help to diVerentiate cerebellar ataxia with and without celiac disease. Methods—Twenty four ataxic patients without definite diagnosis (group A) and 23 ataxic patients with definite diagnosis (group B) were screened for antigliadin (AGAs) and antiendomysium antibodies (EMAs). Patients with a positive AGA or EMA test underwent endoscopic biopsy of the duodenal mucosa. Results—There was an increased prevalence of celiac disease in group A (3/24) compared with group B (0/23). None of the celiac patients presented gastrointestinal symptoms or malabsorption signs. None of the ataxic patients with celiac disease had early onset ataxia. Conclusions—Celiac disease is associated with ataxic syndromes without definite diagnosis, suggesting that it plays a part in the pathogenesis of some ataxic syndromes. The absence of distinctive neurological features in ataxic patients with celiac disease suggests that a search should be made for celiac disease markers in all ataxic patients without definite diagnosis. (J Neurol Neurosurg Psychiatry 1999;66:32‐35)

BACKGROUND AND PURPOSE: The growth hormone (GH) and insulin-like growth factor (IGF) system may be involved in neurodegenerative processes, and some abnormalities have been reported in amyotrophic lateral sclerosis (ALS). Our aim was to investigate the GH-IGF axis in patients with ALS and evaluate correlations between this endocrine system and clinical features. METHODS: Serum levels of GH, IGF-I, IGF-II, insulin, IGF-binding protein 1 (IGF-BP1), and IGF-binding protein 3 (IGF-BP3) were measured in 25 patients with ALS and 25 age-, gender-, and BMI-matched healthy controls. A GHRH plus arginine test was performed in patients and controls. Clinical status of patients was evaluated with the ALS Functional Rating Scale - Revised (ALSFRS-R) and upper motor neuron (UMN) score. RESULTS: GHRH plus arginine test showed GH deficiency (GHD) in 13 (52%) patients with ALS; severe GHD was found in 6 (24%) and partial GHD in 7 (28%) patients. IGF-I levels were significantly higher in patients with ALS than in healthy controls (182.9 +/- 90.8 vs. 139.4 +/- 58.1 ng/ml; P = 0.015). IGF-I levels were higher in patients with ALS with UMN score >10 than those with UMN score

Objective: To investigate whether the presence of parkin gene mutations is associated with different nigrostriatal impairment than other early-onset parkinsonism. Methods: Eighteen consecutive early-onset Parkinson disease (PD) patients (nine parkin and nine nonparkin patients) and six controls were studied with [ 123 I]FP-CIT SPECT. Results: Parkin patients had longer disease duration (15 ± 9 vs 6 ± 2 years, p = 0.008) and higher Unified Parkinson’s Disease Rating Scale (UPDRS) motor score (35.8 ± 13.7 vs 22.8 ± 7.9, p = 0.025) than nonparkin patients. Caudate and putamen DAT density were reduced by 60% and 79% in parkin and by 43% and 70% in nonparkin patients. Multiple regression analysis showed that the UPDRS and the presence of parkin gene mutations, but not the disease duration, were significantly correlated with the striatal DAT density. Parkin patients showed a more symmetric DAT loss in both caudate and putamen as compared with nonparkin patients. Conclusions: Parkin -related disease may be associated with a higher degree of nigrostriatal impairment, independently of the clinical severity of the disease, and a more symmetric involvement as compared with non- parkin early-onset disease.

Clonidine has been proposed to differentiate multiple system atrophy (MSA) from idiopathic Parkinson's disease (IPD), as it does not increase growth hormone (GH) release in MSA. We studied GH release in response to clonidine in 7 IPD patients, 6 MSA patients, 4 patients affected by idiopathic late-onset cerebellar ataxia (ILOCA) and 8 healthy controls. In addition, we investigated the effects of GH releasing hormone plus arginine (GHRH-Arg) on GH release in the same patients. Both clonidine and GHRH-Arg raised serum GH levels in all groups examined. Clonidine failed to differentiate MSA from IPD and ILOCA. GHRH-Arg showed a lower increase of serum GH in MSA patients than in other groups, even if such difference was not statistically significant. We suggest that stimulation of GH release with GHRH-Arg rather than clonidine could differentiate MSA from IPD and ILOCA, but this hypothesis would need to be confirmed by further investigations.

Among male patients affected by Kallmann syndrome, a genetically determined disease due to defective neural migration leading to hypogonadropic hypogonadism and hypo/anosmia, about 40% present the peculiar phenomenon of mirror movements, i.e. involuntary movements mirroring contralateral voluntary hand movements. Several pathogenic hypotheses have been proposed, but the ultimate neurological mechanisms are still elusive. The aim of the present study was to investigate brain anatomical substrates of mirror movements in Kallmann syndrome by means of a panel of quantitative MRI analyses. Forty-nine male Kallmann syndrome patients underwent brain MRI. The study protocol included 3D-T1-weighted gradient echo, fluid attenuated inversion recovery and diffusion tensor imaging. Voxel-based morphometry, sulcation, curvature and cortical thickness analyses and tract based spatial statistics were performed using SPM8, Freesurfer and FSL. All patients underwent a complete physical and neurological examination including the evaluation of mirror movements (according to the Woods and Teuber criteria). Kallmann syndrome patients presenting with mirror movements (16/49, 32%) displayed the following brain changes: 1) increased gray matter density in the depth of the left precentral sulcus behind the middle frontal gyrus; 2) decreased cortical thickness in the precentral gyrus bilaterally, in the depth of right precentral sulcus and in the posterior portion of the right superior frontal gyrus; and 3) decreased fractional anisotropy in the left hemisphere involving the temporal lobe and peritrigonal white matter. No differences were shown by cortical curvature and sulcation analyses. The composite array of brain changes observed in Kallmann syndrome patients with mirror movements likely represents the anatomical-structural underpinnings leading to the peculiar derangement of the complex circuitry committed to unilateral hand voluntary movements.

We describe a patient with clinical signs of parkinsonism showing a paradoxical response to apomorphine injection. We discuss possible pathogenetic mechanisms with regard to the literature and suggest the diagnosis of a striatonigral degeneration at an early stage.

A young man presenting with a Tourette syndrome-like disorder that was the main clinical manifestation of Hallervorden-Spatz syndrome is described. It is recommended that, even in the case of slow progression, HSS should be considered in the differential diagnosis of TS-like disorders.

Objective Multiple system atrophy (MSA) may be difficult to distinguish from idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the arginine growth hormone (GH) stimulation test in distinguishing between MSA and PD in large populations of patients. Methods We measured the GH response to arginine in 69 MSA (43 MSAp [parkinsonism as the main motor feature] and 26 MSAc [cerebellar features predominated]) patients, 35 PD patients, and 90 healthy control subjects. We used receiver-operating curve analysis to establish the arginine cutoff value that best differentiated between MSA and PD. Results The GH response to arginine was significantly lower (p < 0.01) in MSA than in either PD patients or control subjects. At a cutoff level of 4μg/L, arginine distinguished MSAp from PD with a sensitivity and specificity of 91% and MSAc from PD with a sensitivity of 96% and specificity of 91%. The arginine test had a positive predictive value for MSA of 95%. The GH response to arginine was not affected by disease duration or severity, MSA motor subtype, pyramidal signs, response to dopaminergic therapy, or magnetic resonance imaging findings. Interpretation The GH response to arginine differentiates MSA from PD with a high diagnostic accuracy. The results suggest an impairment of cholinergic central systems modulating GH release in MSA. Ann Neurol 2006

Summary Objective Multiple system atrophy (MSA) is difficult to distinguish from idiopathic Parkinson's disease (PD) and idiopathic late-onset cerebellar ataxia (ILOCA). This study aimed to evaluate GH response to three different GH stimulation tests in order to establish a reliable test to differentiate these degenerative disorders. Design Twelve patients with MSA, 10 with PD, eight with ILOCA and 30 healthy controls entered the study. They were submitted to clonidine, arginine, and GH-releasing-hormone (GHRH) + arginine tests in a random manner on three different nonconsecutive days. The peak serum GH response was used as a primary variable for analysis of stimulation tests. By ROC analysis, the optimum cut-off level was considered as the cut-off with the maximal sum of sensitivity and specificity. Results After clonidine administration, GH peak was significantly lower in patients with MSA than in those with ILOCA (P

Thirty patients with Wilson’s disease (WD) were observed at a movement disorder clinic between 1970 and 2000. Disease onset was at the mean age (SD) of 14.5 (±5.9) years. Presentation with hepatic disease occurred in 12 of 30 patients and with neurologic disease in 15. Three patients were asymptomatic at the time of diagnosis. The mean (SD) delay to diagnosis was 5.9 (±5.7) years. Five patients diagnosed in an advanced stage of disease died before initiating treatment. Eighteen patients were followed and treated with D-penicillamine alone or in combination with zinc sulphate. Treatment improved most of neurological symptoms. Dystonic postures, behavioural disturbances and dysarthria were the most resistant neurological signs. ‘Pseudo-sclerotic’ neurologic involvement predicted a good outcome, whereas hepatic onset and ‘classic’ neurologic involvement were associated with a poorer prognosis. Two of the 18 treated patients died of hepatic failure due to voluntary discontinuation of therapy. Both D-penicillamine and zinc sulphate were well tolerated. No teratogenic effect of D-penicillamine was observed throughout 5 pregnancies. Our results suggest that D-penicillamine or a combination of D-penicillamine and zinc sulphate is a safe and effective long-term treatment in patients with WD.

Wellcome Trust/MRC Joint Call in Neurodegeneration award United Kingdom Medical Research Council Wellcome Trust Parkinson's Disease UK Kattan Trust Objectives: To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.Methods: A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. the right: left asymmetry index and striatal asymmetry index was calculated.Results: Scans were available from 37 cases of monogenetic Parkinson's disease (7 glucocerebrosidase (GBA) mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin). the asymmetry of radioligand uptake for Parkinson's disease with GBA or LRRK2 mutations was greater than that for Parkinson's disease with alpha synuclein, PINK1 or Parkin mutations.Conclusions: the asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss. UCL, Dept Clin Neurosci, Inst Neurol, London, England Birmingham Womens Hosp, Reg Genet Unit, Dept Clin Genet, Birmingham, W Midlands, England Natl Taiwan Univ Hosp, Coll Med, Dept Neurol, Taipei, Taiwan Natl Taiwan Univ Hosp, Coll Med, Dept Nucl Med, Taipei, Taiwan Hosp Israelita Albert Einstein, Inst Israelita Ensino & Pesquisa Albert Einstein, São Paulo, Brazil Hosp Univ Insular Gran Canaria, Dept Neurol, Parkinsons & Movement Disorders Unit, Las Palmas Gran Canaria, Spain Univ Salerno, Ctr Neurodegenerat Dis, Salerno, Fisciano Provin, Italy UCL, Inst Neurol, Sobell Dept Motor Sci, London, England Universidade Federal de São Paulo, Dept Neurol, São Paulo, Brazil Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands Aristotle Univ Thessaloniki, G Papanikolaou Hosp, Dept Neurol 3, GR-54006 Thessaloniki, Greece Gen Hosp S Michele AOB G Brotzu, Neurol Serv, Cagliari, Italy Gen Hosp S Michele AOB G Brotzu, Stroke Unit, Cagliari, Italy Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy Universidade Federal de São Paulo UNIFESP, EPM, Div Movement Disorders, São Paulo, Brazil UCL Inst Neurol, Dept Mol Neurosci, London, England Univ Navarra, Div Neurosci, Ctr Appl Med Res, Neurogenet Lab, E-31080 Pamplona, Spain CNR, Inst Biostruct & Bioimaging, I-80125 Naples, Italy Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden Universidade Federal de São Paulo, Dept Neurol, São Paulo, Brazil Universidade Federal de São Paulo UNIFESP, EPM, Div Movement Disorders, São Paulo, Brazil Wellcome Trust/MRC Joint Call in Neurodegeneration award: WT089698 United Kingdom Medical Research Council: G1001983 Web of Science