Negative symptoms in Huntington's disease.

BACKGROUND: Apathy is the commonest psychiatric manifestation in Huntington's disease (HD). We investigated negative psychiatric symptoms-as determined by the Scale for the Assessment of Negative Psychiatric Symptoms (SANS)-in early and intermediate HD patients, hypothesizing that such symptoms would be prominent and constitute a more comprehensive and clinically relevant assessment than apathy alone. We also assessed relations between negative symptoms and disease stage, mood, motor, and cognitive disturbances. METHODS: Thirty-five stage 1 and twenty-nine stage 2 consecutive adult HD outpatients were administered SANS; the Scale for the Assessment of Positive Psychiatric Symptoms (SAPS); the motor section of the Unified Huntington's Disease Rating Scale (UHDRS); Total Functional Capacity (TFC); and instruments to assess cognition, anxiety, and depression. RESULTS: The groups had similar age, education, and CAG length. Scores on the Hamilton depression and anxiety scales, and SAPS were similar. Negative symptoms were pervasive in the entire series. Illness duration, UHDRS, TFC, cognition, and SANS scores were significantly worse in stage 2. Mini Mental State Examination (MMSE) and SAPS scores were significantly (multiple regression) associated with SANS score, while Hamilton depression and UHDRS scores were not. SANS score was also associated with stage after removing the cognition-related domains of alogia and attention. CONCLUSIONS: Negative symptoms are pervasive in HD but more severe in stage 2. The associations of SANS with MMSE and SAPS suggest impaired cognition and thinking as important in generating negative symptoms. SANS appears useful for revealing a wide range of negative symptoms in HD.

Geographic differences in the incidence of Huntington's disease in Sardinia, Italy.

BACKGROUND: The frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non-Asian populations. We have recently examined the prevalence of HD in the southern part of Sardinia, a large Italian Mediterranean island that is considered a genetic isolate. We observed regional microgeographic differences in the prevalence of HD across the study area similar to those recently reported in other studies conducted in European countries. To explore the basis for this variability, we undertook a study of the incidence of HD in Sardinia over a 10-year period, 2009 to 2018. METHODS: Our research was conducted in the 5 administrative areas of Sardinia island. Case patients were ascertained through multiple sources in Sardinia and Italy. RESULTS: During the incidence period 53 individuals were diagnosed with clinically manifested HD. The average annual incidence rate 2009-2018 was 2.92 per 106 persons-year (95% CI, 2.2 to 3.9). The highest incidence rate was observed in South Sardinia (6.3; 95% CI, 4.2-9.5). This rate was significantly higher (p<0.01) than the rates from Cagliari, Oristano, and Sassari provinces but did not significantly differ (p = 0.38) from the Nuoro rate. CONCLUSIONS: The overall incidence of HD in Sardinia is close to the correspondent estimates in Mediterranean countries. Our findings highlight also the possibility of local microgeographic variations in the epidemiology of HD that might reflect several factors, including a possible founder effect in the rural areas of South Sardinia and Nuoro.

Overlapping phenotypes in complex spastic paraplegias SPG11, SPG15, SPG35 and SPG48.

Hereditary spastic paraplegias are a heterogeneous group of neurodegenerative disorders, clinically classified in pure and complex forms. Genetically, more than 70 different forms of spastic paraplegias have been characterized. A subgroup of complicate recessive forms has been distinguished for the presence of thin corpus callosum and white matter lesions at brain imaging. This group includes several genetic entities, but most of the cases are caused by mutations in the KIAA1840 (SPG11) and ZFYVE26 genes (SPG15). We studied a cohort of 61 consecutive patients with complicated spastic paraplegias, presenting at least one of the following features: mental retardation, thin corpus callosum and/or white matter lesions. DNA samples were screened for mutations in the SPG11/KIAA1840, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG48/AP5Z1 and SPG54/DDHD2 genes by direct sequencing. Sequence variants were found in 30 of 61 cases: 16 patients carried SPG11/KIAA1840 gene variants (26.2%), nine patients carried SPG15/ZFYVE26 variants (14.8%), three patients SPG35/FA2H (5%), and two patients carried SPG48/AP5Z1 gene variants (3%). Mean age at onset was similar in patients with SPG11 and with SPG15 (range 11-36), and the phenotype was mostly indistinguishable. Extrapyramidal signs were observed only in patients with SPG15, and epilepsy in three subjects with SPG11. Motor axonal neuropathy was found in 60% of cases with SPG11 and 70% of cases with SPG15. Subjects with SPG35 had intellectual impairment, spastic paraplegia, thin corpus callosum, white matter hyperintensities, and cerebellar atrophy. Two families had a late-onset presentation, and none had signs of brain iron accumulation. The patients with SPG48 were a 5-year-old child, homozygous for a missense SPG48/AP5Z1 variant, and a 51-year-old female, carrying two different nonsense variants. Both patients had intellectual deficits, thin corpus callosum and white matter lesions. None of the cases in our cohort carried mutations in the SPG21/ACP33 and SPG54/DDH2H genes. Our study confirms that the phenotype of patients with SPG11 and with SPG15 is homogeneous, whereas cases with SPG35 and with SPG48 cases present overlapping features, and a broader clinical spectrum. The large group of non-diagnosed subjects (51%) suggests further genetic heterogeneity. The observation of common clinical features in association with defects in different causative genes, suggest a general vulnerability of the corticospinal tract axons to a wide spectrum of cellular alterations.

Capgras delusion for animals and inanimate objects in Parkinson's Disease: a case report.

BACKGROUND: Capgras delusion is a delusional misidentification syndrome, in which the patient is convinced that someone that is well known to them, usually a close relative, has been replaced by an impostor or double. Although it has been frequently described in psychotic syndromes, including paranoid schizophrenia, over a third of the documented cases of Capgras delusion are observed in patients with organic brain lesions or neurodegenerative disease, including Parkinson's Disease. Variants of Capgras involving animals or inanimate objects have also been described. The etiology of Capgras in Parkinson's remains unclear, but may arise from a combination of factors, such as frontal lobe dysfunction and dopaminergic medication. CASE PRESENTATION: We present the case of a 53-year old right-handed female with Parkinson's disease who developed Capgras delusion during treatment with dopamine agonists and Levodopa/Carbidopa. She became convinced that her pet dogs and the plants in her garden had been substituted by identically looking ones. Our patient was initially treated with Quetiapine, with no improvement, and subsequently treated with Clozapine, which lead to partial regression of her symptoms. Neuropsychological Evaluation showed Mild Cognitive Impairment in Executive Functions. CONCLUSIONS: Given the clinical history, onset and evolution of symptoms we believe our patient's delusion resulted from the overlap of dopaminergic medication and Mild Cognitive Impairment in executive functions. Zoocentric Capgras, the variant we describe, has been rarely described in scientific literature, and we believe it is of interest due to its unusual characteristics.

The Clinical Spectrum of ANO3-Report of a New Family and Literature Review.

BACKGROUND: Mutations in ANO3 are a rare cause of autosomal dominant isolated or combined dystonia, mainly presenting in adulthood. CASES: We extensively characterize a new, large ANO3 family with six affected carriers. The proband is a young girl who had suffered from tremor and painful dystonic movements in her right arm since the age of 11 years. She later developed a diffuse dystonic tremor and mild extrapyramidal signs (ie, rigidity and hypodiadochokinesis) in her right arm. She also suffered from psychomotor delay and learning difficulties. Repeated structural and functional neuroimaging were unremarkable. A dystonic tremor was also present in her two sisters. Her paternal aunt, father, and a third older sister presented episodic postural tremor in the arms. The father and one sister also presented learning difficulties. The heterozygous p.G6V variant in ANO3 was identified in all affected subjects. LITERATURE REVIEW: Stratification by age at onset divided ANO3 cases into two major groups, where younger patients displayed a more severe phenotype, probably due to variants near the scrambling domain. CONCLUSIONS: We describe the phenotype of a new ANO3 family and highlight the need for functional studies to explore the impact of ANO3 variants on its phospholipid scrambling activity.

Onset and mortality of Parkinson's disease in relation to type II diabetes.

OBJECTIVES: There is growing evidence that Parkinson's disease and diabetes are partially related diseases; however, the association between the two, and the impact of specific treatments, are still unclear. We evaluated the effect of T2D and antidiabetic treatment on age at PD onset and on all-cause mortality. RESEARCH DESIGN AND METHODS: The standardized rate of T2D was calculated for PD patients using the direct method and compared with subjects with essential tremor (ET) and the general Italian population. Age at onset and survival were also compared between patients without T2D (PD-noT2D), patients who developed T2D before PD onset (PD-preT2D) and patients who developed T2D after PD onset (PD-postT2D). RESULTS: We designed a retrospective and prospective study. The T2D standardized ratio of PD (N = 8380) and ET (N = 1032) patients was 3.8% and 6.1%, respectively, while in the Italian general population, the overall prevalence was 5.3%. In PD-preT2D patients, on antidiabetic treatment, the onset of PD was associated with a + 6.2 year delay (p < 0.001) while no difference was observed in PD-postT2D. Occurrence of T2D before PD onset negatively affected prognosis (adjusted hazard ratio = 1.64 [95% CI 1.33-2.02]; p < 0.001), while no effect on survival was found in PD-postT2D subjects (hazard ratio = 0.86, [95% CI 0.53-1.39]; p = 0.54). CONCLUSIONS: T2D, treated with any antidiabetic therapy before PD, is associated with a delay in its onset. Duration of diabetes increases mortality in PD-preT2D, but not in PD-postT2D. These findings prompt further studies on antidiabetic drugs as a potential disease-modifying therapy for PD.

Concordance between severity of disease, prevalence of nonmotor symptoms, patient-reported quality of life and disability and use of medication in Parkinson's disease.

The aim of this study was to test the concordance between disease severity, prevalence of nonmotor symptoms, age, health-related quality of life (HRQoL), disability and medication use in patients with Parkinson's disease (PD). Severity was classified with the Hoehn and Yahr (HY) scale and Levodopa Equivalent Daily Dose (LEDD) calculated. HRQoL was evaluated with the SF-36, disability with the WHO-DAS II and nonmotor symptoms with the NMSQuest. Patients were clustered using SF-36 and WHO-DAS II into three groups covering the continuum from low disability and HRQoL, to severe disability and HRQoL decrement. Contingency Coefficient were used to verify the relationships between clusters and HY stage; ANOVA to evaluate differences in NMS, age and LEDD between clusters; odds ratio to test the likelihood of taking levodopa or dopamine agonist and being member of the three clusters; t test to evaluate differences in LEDD between patients with HY ≥3 or ≤2. Eighty-six patients were clustered: 48 had low disability and HRQoL decrement, 18 intermediate disability and HRQoL decrement and 20 high disability and HRQoL decrement. A significant relationship was found between PD severity groups, HRQoL and disability profiles. No differences for age and LEDD were observed in the three groups, and those with more disability and lower HRQoL reported a higher number of nonmotor symptoms; patients in HY ≥3 were prescribed higher doses of drugs. In conclusion, we found a substantial concordance between PD staging, prevalence of nonmotor symptoms and patient-reported HRQoL and disability measures. In our opinion, the SF-36 and the WHO-DAS II can be used for profiling patients.

Long-term safety, discontinuation and mortality in an Italian cohort with advanced Parkinson's disease on levodopa/carbidopa intestinal gel infusion.

INTRODUCTION: Levodopa/carbidopa intestinal gel (LCIG) is an effective treatment in patients with advanced Parkinson's disease (PD) with consolidated evidence of clinical efficacy. However, only few studies have assessed long-term safety, causes of discontinuation, mortality, and relative predictors. METHODS: We conducted a retrospective analysis of 79 PD patients treated with LCIG between 2005 and 2020 in two Italian Neurological Centers, recording all adverse events (AEs), including weight loss (WL). Kaplan-Meier curve was used to estimate the time to discontinuation and survival. Cox proportional hazard model was employed to identify predictors of discontinuation and mortality, while Pearson's correlation was used to analyze predictors of WL. RESULTS: The average follow-up was 47.7 ± 40.5 months and the median survival from disease onset was 25 years. There were three cases of polyradiculoneuropathy Guillain-Barre syndrome-like, all occurred in the early years of LCIG treatment. Twenty-five patients died (32%), 18 on LCIG (including one suicide) and seven after discontinuation. The mean WL was 3.62 ± 7.5 kg, which correlated with levodopa dose at baseline (p = 0.002), levodopa equivalent daily dose (LEDD) baseline (p = 0.017) and off-duration (p = 0.0014), but not dyskinesia. Peristomal complications emerged as a negative predictor of discontinuation (p = 0.008). CONCLUSIONS: LCIG has a relatively satisfactory long-term safety profile and efficacy and a relatively low rate of discontinuation. Peristomal complications may represent a predictor of longer duration of therapy. According to the mortality analysis, LCIG patients show a long lifespan. Delaying the initiation of LCIG does not affect the sustainability of LCIG therapy.

Adult-onset KMT2B-related dystonia.

KMT2B-related dystonia (DYT-KMT2B, also known as DYT28) is an autosomal dominant neurological disorder characterized by varying combinations of generalized dystonia, psychomotor developmental delay, mild-to-moderate intellectual disability and short stature. Disease onset occurs typically before 10 years of age. We report the clinical and genetic findings of a series of subjects affected by adult-onset dystonia, hearing loss or intellectual disability carrying rare heterozygous KMT2B variants. Twelve cases from five unrelated families carrying four rare KMT2B missense variants predicted to impact protein function are described. Seven affected subjects presented with adult-onset focal or segmental dystonia, three developed isolated progressive hearing loss, and one displayed intellectual disability and short stature. Genome-wide DNA methylation profiling allowed to discriminate these adult-onset dystonia cases from controls and early-onset DYT-KMT2B patients. These findings document the relevance of KMT2B variants as a potential genetic determinant of adult-onset dystonia and prompt to further characterize KMT2B carriers investigating non-dystonic features.

In vivo evidence for GABA(A) receptor changes in the sensorimotor system in primary dystonia.

BACKGROUND: Preclinical and clinical evidence suggests that impaired gamma-aminobutyric (GABA) control, leading to disinhibition within the sensorimotor system, might play a role in dystonia. Aim of this study is the in vivo assessment of the GABAergic system in dystonia using positron emission tomography (PET) and (11) C-flumazenil, a selective GABA(A) receptor ligand. METHODS: Fourteen subjects with primary dystonia (9 carriers of the DYT1 mutation and 5 sporadic cases) were compared to 11 controls, using a simplified reference tissue model to measure binding potential. RESULTS: Voxel-based analyses showed a reduction in GABA(A) receptor expression/affinity both in DYT1 carriers and sporadic patients in primary motor and premotor cortex, primary and secondary somatosensory cortex, and in the motor component of the cingulate gyrus. CONCLUSIONS: Dysfunction of GABA(A) receptors in sensorimotor systems in primary (genetic and sporadic) dystonia supports the view that lack of GABAergic control may be associated with the generation of dystonic movements.

Childhood-onset dystonia-causing KMT2B variants result in a distinctive genomic hypermethylation profile.

BACKGROUND: Dystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements and/or postures. Heterozygous variants in lysine methyltransferase 2B (KMT2B), encoding a histone H3 methyltransferase, have been associated with a childhood-onset, progressive and complex form of dystonia (dystonia 28, DYT28). Since 2016, more than one hundred rare KMT2B variants have been reported, including frameshift, nonsense, splice site, missense and other in-frame changes, many having an uncertain clinical impact. RESULTS: We characterize the genome-wide peripheral blood DNA methylation profiles of a cohort of 18 patients with pathogenic and unclassified KMT2B variants. We resolve the "episignature" associated with KMT2B haploinsufficiency, proving that this approach is robust in diagnosing clinically unsolved cases, properly classifying them with respect to other partially overlapping dystonic phenotypes, other rare neurodevelopmental disorders and healthy controls. Notably, defective KMT2B function in DYT28 causes a non-random DNA hypermethylation across the genome, selectively involving promoters and other regulatory regions positively controlling gene expression. CONCLUSIONS: We demonstrate a distinctive DNA hypermethylation pattern associated with DYT28, provide an epigenetic signature for this disorder enabling accurate diagnosis and reclassification of ambiguous genetic findings and suggest potential therapeutic approaches.

Impaired awareness of movement disorders in Parkinson's disease.

BACKGROUND: This study analyzed the presence of awareness of movement disorders (dyskinesias and hypokinesias) in 25 patients with Parkinson's disease (PD) and motor fluctuations (dyskinesias, wearing off, on-off fluctuations). Of the few studies that have dealt with this topic, none have analyzed the differences in the awareness of motor deficits by comparing the on and off states using motor scales and an extensive battery of tests to assess cognitive and behavioral functioning. METHODS: PD patients were compared on three different scales that we have devised to measure awareness of movement disorders: Global Awareness of Movement (GAM) Disorders, dyskinesia/hypo-bradykinesia rating scales. RESULTS: Data showed that PD patients had greater awareness and psychological suffering in the off state than in the on state. In particular, they were troubled by motor disabilities related to hypokinesias and had mood-related symptoms and a perception of disability in activities of daily living. Interestingly, patients only showed a selective reduction of awareness of movement disorders associated with executive functions and related to dyskinesias in the on state, compared to a preserved awareness of hypokinesias in the off state. On the contrary, no association with executive functions was found in the off state. CONCLUSION: Our findings suggest that the dopaminergic overstimulation of mesocorticolimbic pathways may cause a dysfunction of prefrontal-subcortical connections related to the impaired insight.

Prevalence of Huntington's disease in Southern Sardinia, Italy.

BACKGROUND: The frequency of Huntington's disease (HD) may vary considerably, with higher estimates in non Asian populations. In Italy, two recent studies performed in Ferrara county and Molise provided different prevalence estimates, varying from 4.2 × 105 to 10.8 × 105. Here we present a study performed in the Southern part of Sardinia, a large Italian mediterranean island that is considered a genetic isolate. METHODS: The study area included the two neighbouring counties of South Sardinia and Cagliari with 353,830 and 431,955 inhabitants respectively on December 31st, 2017 (prevalence date). Case-patients were ascertained through multiple sources in Sardinia and Italy. RESULTS: We identified 54 individuals with HD, of whom 47 were alive on prevalence date. The resulting prevalence rate was 5.98 × 105 in the overall study area, however with marked variations between South Sardinia and Cagliari (9.6 × 105 vs. 3.0 × 105, p = 0.02). In the two study areas, we found similar CAG repeat length in normal alleles (17.5 ± 2.1 vs. 17.7 ± 2.2, p = 0.5). CONCLUSIONS: The overall prevalence of HD in Sardinia is close to the correspondent estimates in Europeans. Our findings also highlighted the possibility of local microgeographic variations in the epidemiology of HD.

ICF in neurology: functioning and disability in patients with migraine, myasthenia gravis and Parkinson's disease.

PURPOSE: To report and compare functional features of patients with migraine, myasthenia gravis (MG) and Parkinson's disease (PD) with the International Classification of Functioning, Disability and Health (ICF). METHOD: Adult patients with migraine, MG and PD were enrolled and the ICF checklist administered. Count-based indexes were calculated for each ICF chapter and domain. Indexes were compared across conditions by means of ANOVA; relationships between ICF domains were evaluated using Spearman's correlation; group based on disability status were defined through cluster analysis and compared with disease groups using chi(2) test. Finally, most prevalent ICF categories were identified. RESULTS: A total of 300 patients were enrolled and specific differences in BF, BS, A&P and EF indexes are reported. Spearman's correlations reported moderate relationships between BF and A&P indexes, whereas the correlation between A&P and EF is lower. Cluster analysis and chi(2) test show that patients with Migraine and MG are more likely to report moderate and low disability, whereas patients with PD are more likely to report moderate or severe disability. A total of 60 ICF relevant categories, mostly from A&P, were identified. CONCLUSIONS: Our study provided a description of functioning and disability domains in migraine, MG and PD and enabled to report the impact of EF in determining the actual disability experience.

Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson's disease and multiple system atrophy.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder whose diagnosis is often challenging because symptoms may overlap with neurodegenerative parkinsonisms. PD is characterized by intraneuronal accumulation of abnormal α-synuclein in brainstem while neurodegenerative parkinsonisms might be associated with accumulation of either α-synuclein, as in the case of Multiple System Atrophy (MSA) or tau, as in the case of Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP), in other disease-specific brain regions. Definite diagnosis of all these diseases can be formulated only neuropathologically by detection and localization of α-synuclein or tau aggregates in the brain. Compelling evidence suggests that trace-amount of these proteins can appear in peripheral tissues, including receptor neurons of the olfactory mucosa (OM). METHODS: We have set and standardized the experimental conditions to extend the ultrasensitive Real Time Quaking Induced Conversion (RT-QuIC) assay for OM analysis. In particular, by using human recombinant α-synuclein as substrate of reaction, we have assessed the ability of OM collected from patients with clinical diagnoses of PD and MSA to induce α-synuclein aggregation, and compared their seeding ability to that of OM samples collected from patients with clinical diagnoses of CBD and PSP. RESULTS: Our results showed that a significant percentage of MSA and PD samples induced α-synuclein aggregation with high efficiency, but also few samples of patients with the clinical diagnosis of CBD and PSP caused the same effect. Notably, the final RT-QuIC aggregates obtained from MSA and PD samples owned peculiar biochemical and morphological features potentially enabling their discrimination. CONCLUSIONS: Our study provide the proof-of-concept that olfactory mucosa samples collected from patients with PD and MSA possess important seeding activities for α-synuclein. Additional studies are required for (i) estimating sensitivity and specificity of the technique and for (ii) evaluating its application for the diagnosis of PD and neurodegenerative parkinsonisms. RT-QuIC analyses of OM and cerebrospinal fluid (CSF) can be combined with the aim of increasing the overall diagnostic accuracy of these diseases, especially in the early stages.

A neurophysiological study of myoclonus in patients with DYT11 myoclonus-dystonia syndrome.

Mutations in the epsilon-sarcoglycan (SGCE) gene have been associated with DYT11 myoclonus-dystonia syndrome (MDS). The aim of this study was to characterize myoclonus in 9 patients with DYT11-MDS presenting with predominant myoclonus and mild dystonia by means of neurophysiological techniques. Variously severe multifocal myoclonus occurred in all of the patients, and included short (mean 89.1 +/- 13.3 milliseconds) electromyographic bursts without any electroencephalographic correlate, sometimes presenting a pseudo-rhythmic course. Massive jerks could be evoked by sudden stimuli in 5 patients, showing a "startle-like" muscle spreading and latencies consistent with a brainstem origin. Somatosensory evoked potentials and long-loop reflexes were normal, as was silent period and long-term intracortical inhibition evaluated by means of transcranial magnetic stimulation; however, short-term intracortical inhibition revealed subtle impairment, and event-related synchronization (ERS) in the beta band was delayed. Blink reflex recovery was strongly enhanced. Myoclonus in DYT11-MDS seems to be generated at subcortical level, and possibly involves basal ganglia and brainstem circuitries. Cortical impairment may depend from subcortical dysfunction, but it can also have a role in influencing the myoclonic presentation. The wide distribution of the defective SCGE in DYT11-MDS may justify the involvement of different brain areas.

Stereotypic behaviours in frontotemporal dementia and progressive supranuclear palsy.

INTRODUCTION: The behavioural variant of frontotemporal dementia (bvFTD), and the Richardson variant of progressive supranuclear palsy (PSP-RS) share several clinical signs and symptoms. Since stereotypic behaviours are fairly common in bvFTD, and are also described in other degenerative dementias including Alzheimer's disease, and parkinsonisms with dementia, we aimed to examine the extent to which stereotypies also characterise PSP-RS. METHODS: We compared 53 bvFTD patients with 40 demented PSP-RS patients, seen consecutively as outpatients at four Italian Hospitals. Patients were assessed by the Neuropsychiatric Inventory (NPI); Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) for cognitive functions; Stereotypy Rating Inventory (SRI) for stereotypies; Unified Parkinson's Disease Rating Scale (UPDRS) for motor function; and Activities of Daily Living (ADL) to assess autonomy in daily life. RESULTS: The groups did not differ for age, illness duration, cognitive functions or total NPI score; PSP-RS had significantly more depressive symptoms and greater motor and autonomy compromise than bvFTD. The groups did not differ significantly on total SRI score, but bvFTD had significantly more cooking and eating stereotypies. Twenty-three (57.5%) PSP-RS and 43 (81%) bvFTD patients had at least one stereotypy; 16/23 (69.5%) PSP-RS and 9/43 (20.9%) bvFTD patients appeared aware of their stereotypies. CONCLUSION: Stereotypies were common in our demented PSP-RS patients. Further studies on earlier stage non-demented PSP patients are required to ascertain whether stereotypies are characteristic of PSP in general or are confined to PSP-RS, and whether they may be used to suggest a PSP diagnosis early in disease course.

Spinocerebellar ataxia type 17 (SCA17): oculomotor phenotype and clinical characterization of 15 Italian patients.

SCA17 is a rare type of autosomal dominant spinocerebellar ataxia caused by a CAG/CAA expansion in the gene encoding the TATA-binding protein (TBP). We screened for triplet expansion in the TBP gene 110 subjects with progressive cerebellar ataxia and 94 subjects with Huntington-like phenotype negative at specific molecular tests. SCA17 mutation-positive subjects were found in both groups of patients. Expanded alleles with > or = 44 CAG/CAA repeats were identified in 11 individuals and in 4 non-symptomatic relatives. Eleven de novo diagnosed patients and four patients previously reported underwent extensive clinical, neuroradiological and oculographic examination. Cerebellar signs and symptoms were present in all cases; 80% of the patients had mild to severe cognitive deficits; 66% of patients showed choreic movements; pyramidal signs, bradykinesia and dystonia were observed in approx 50% of the cases. MRI demonstrated cortical and cerebellar atrophy in all patients, whereas neurophysiological examination excluded signs of peripheral nervous system involvement. Oculographic examinations were performed in 9 out of 15 patients and showed a distinct pattern of oculomotor abnormalities, characterized by impairment of smooth pursuit, defects in the saccade accuracy, normal saccade velocity, hyperreflexia of vestibuloocular reflexes, and absence of nystagmus. In summary, this study presents one of the largest series of SCA17 patients in Europe. In our group of patients, SCA17 represents the third most frequent SCA genotype. Our clinical data confirm the large variability in SCA17 phenotypic presentation, and indicate that a peculiar combination of neuroradiological, electrophysiological and oculomotor findings is recognizable in SCA17.

Psychosocial difficulties in patients with Parkinson's disease.

The aim of this study was to report the most frequent psychosocial difficulties (PSDs) in patients with Parkinson disease (PD), to explore the relationship between PSDs, disability and quality of life (QoL), and to address the predictors of PSDs. Patients with PD were interviewed using a protocol composed of a questionnaire investigating PSDs (PARADISE 24), QoL, disability, comorbidity, and social support questionnaires, scales on resilience, personality traits, and empathy in physician. Most frequent PSDs were reported. Spearman's correlation was used to address the relationship between PARADISE 24 and QoL and disability measures. Multiple linear regression was performed to investigate predictors of PARADISE 24. Eighty patients were enrolled: 40% women, mean age 61.2 years. The most frequent PSDs were related to cognitive and motor slowness, tiredness, sleeping, facing all things to do, depressive mood, and anxiety. PARADISE 24 were correlated with disability (ρ=0.831) and QoL (ρ=-0.685). Lower QoL, higher disability, early age at onset, and shorter disease duration were significant predictors of PSDs (adjusted R=0.762). PARADISE 24 is an easy to use questionnaire that could contribute toward describing the impact of PD on patients' life more extensively, thus helping to define more tailored interventions.