Pisa syndrome in Idiopathic Normal Pressure Hydrocephalus.

Abstract Introduction Idiopathic Normal Pressure Hydrocephalus (iNPH) is a complex syndrome of ventriculomegaly that can include parkinsonian-like features besides the classical triad of cognitive decline, urinary incontinence, and gait/balance disturbances. Pisa syndrome (PS) is a postural abnormality often associated with parkinsonism and defined as lateral trunk flexion greater than 10° while standing that resolves in the supine position. We reported a case series of classical "fixed" PS and one case of "Metronome" recurrent side-alternating PS in iNPH, displaying opposite electromyographic patterns of paraspinal muscles. Methods Eighty-five iNPH patients were followed longitudinally for at least one year through scheduled clinical and neuropsychological visits. Results Five (5.9%) subjects revealed PS. None of them had nigrostriatal dopaminergic involvement detected by [123I]FP-CIT SPECT. Among these patients, four had "fixed" PS, whereas one showed a recurrent side-alternating PS which repeatedly improved after ventriculo-peritoneal shunt and following adjustments of the valve-opening pressure of the shunt system. Discussion This is the first case series of PS in iNPH and the first report of "Metronome" PS in iNPH. The prompt response of the abnormal trunk postures through cerebrospinal fluid (CSF) shunt surgery suggests a causative role of an altered CSF dynamics. PS and gait disorders in iNPH could be explained by a direct involvement of cortico-subcortical pathways and subsequent secondary brainstem involvement, with also a possible direct functional damage of the basal ganglia at the postsynaptic level, due to enlargement of the ventricular system and impaired CSF dynamics. The early detection of these cases supports a proper surgical management

Diagnostic accuracy of quantitative susceptibility mapping in multiple system atrophy: The impact of echo time and the potential of histogram analysis

The non-invasive quantification of iron stores via Quantitative Susceptibility Mapping (QSM) could play an important role in the diagnosis and the differential diagnosis of atypical Parkinsonisms. However, the susceptibility (χ) values measured via QSM depend on echo time (TE). This effect relates to the microstructural organization within the voxel, whose composition can be altered by the disease. Moreover, pathological iron deposition in a brain area may not be spatially uniform, and conventional Region of Interest (ROI)-based analysis may fail in detecting alterations. Therefore, in this work we evaluated the impact of echo time on the diagnostic accuracy of QSM on a population of patients with Multiple System Atrophy (MSA) of either Parkinsonian (MSAp) or cerebellar (MSAc) phenotypes. In addition, we tested the potential of histogram analysis to improve QSM classification accuracy. We enrolled 32 patients (19 MSAp and 13 MSAc) and 16 healthy controls, who underwent a 7T MRI session including a gradient-recalled multi-echo sequence for χ mapping. Nine histogram features were extracted from the χ maps computed for each TE in atlas-based ROIs covering deep brain nuclei, and compared among groups. Alterations of susceptibility distribution were found in the Putamen, Substantia Nigra, Globus Pallidus and Caudate Nucleus for MSAp and in the Substantia Nigra and Dentate Nucleus for MSAc. Increased iron deposition was observed in a larger number of ROIs for the two shortest TEs and the standard deviation, the 75th and the 90th percentile were the most informative features yielding excellent diagnostic accuracy with area under the ROC curve > 0.9. In conclusion, short TEs may enhance QSM diagnostic performances, as they can capture variations in rapidly-decaying contributions of high χ sources. The analysis of histogram features allowed to reveal fine heterogeneities in the spatial distribution of susceptibility alteration, otherwise undetected by a simple evaluation of ROI χ mean values

A review of cognitive impairment and differential diagnosis in idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a complex and still underestimated pathology. In the early stages, the cognitive profile is characterized mainly by impairments of attention, psychomotor speed and memory, suggesting frontal involvement; patients with more advanced iNPH show overall cognitive deterioration. The memory impairment, however, seems to be milder than that seen in Alzheimer’s disease (AD). Clinical and neuroimaging data are crucial for the diagnosis of iNPH, but the presence of different variables, such as comorbidities, and the possible overlapping with other neurodegenerative diseases, AD in particular, make the differential diagnosis difficult. To date studies seeking to identify possible biological markers have provided inconclusive results; moreover reliable indices predictive of a good response to surgery are still lacking. There is a need for further studies with longer follow-ups and for closer interaction among the different professionals involved

α-Synuclein antisense transcript SNCA-AS1 regulates synapses- and aging-related genes suggesting its implication in Parkinson's disease

SNCA protein product, α‐synuclein, is widely renowned for its role in synaptogenesis and implication in both aging and Parkinson's disease (PD), but research efforts are still needed to elucidate its physiological functions and mechanisms of regulation. In this work, we aim to characterize SNCA‐AS1, antisense transcript to the SNCA gene, and its implications in cellular processes. The overexpression of SNCA‐AS1 upregulates both SNCA and α‐synuclein and, through RNA‐sequencing analysis, we investigated the transcriptomic changes of which both genes are responsible. We highlight how they impact neurites' extension and synapses' biology, through specific molecular signatures. We report a reduced expression of markers associated with synaptic plasticity, and we specifically focus on GABAergic and dopaminergic synapses, for their relevance in aging processes and PD, respectively. A reduction in SNCA‐AS1 expression leads to the opposite effect. As part of this signature is co‐regulated by the two genes, we discriminate between functions elicited by genes specifically altered by SNCA‐AS1 or SNCA's overexpression, observing a relevant role for SNCA‐AS1 in synaptogenesis through a shared molecular signature with SNCA. We also highlight how numerous deregulated pathways are implicated in aging‐related processes, suggesting that SNCA‐AS1 could be a key player in cellular senescence, with implications for aging‐related diseases. Indeed, the upregulation of SNCA‐AS1 leads to alterations in numerous PD‐specific genes, with an impact highly comparable to that of SNCA's upregulation. Our results show that SNCA‐AS1 elicits its cellular functions through the regulation of SNCA, with a specific modulation of synaptogenesis and senescence, presenting implications in PD

REM and NREM sleep enactment behaviors in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies

none8Background/objective: Nocturnal sleep enactment behaviors (SEBs) are common in patients affected by Parkinson's disease (PD), dementia associated with Parkinson's disease (PDD), and dementia with Lewy bodies (DLB). We investigated the occurrence and neurobiological significance of abnormal SEBs in the context of PD without cognitive decline compared to PDD/DLB patients. Methods: We evaluated a sample of 139 patients with PD, PDD, or DLB in a cross-sectional survey. One hundred and seventeen patients showing either no cognitive impairment (PD group) or meeting the diagnostic requirements for dementia (PDD/DLB group) underwent video-polysomnography. Seventy subjects (42 males) in whom a clear-cut diagnosis of abnormal sleep-related motor-behavioral episodes was possible were included in the final analysis. Results: SEBs consisting of RBD or occurring on arousal from NREM or REM sleep were globally more frequent in the dementia group (PDD/DLB) than in the PD group (p= 0.001), the difference being statistically significant for arousal-related episodes (p= 0.002), while a trend emerged for RBD (p= 0.07). Male sex, daytime sleepiness, higher motor impairment, and lower mini-mental score were significantly more frequent with the occurrence of abnormal sleep-related motor-behavioral episodes. Conclusion: SEBs in PD, PDD, and DLB may consist of RBD episodes or of arousal-related NREM and REM episodes. These latter are more frequent in patients with PDD/DLB and seem to be mainly related to more advanced stages of disease with a higher degree of cognitive decline. © 2012 Elsevier B.V.noneRatti P.-L.; Terzaghi M.; Minafra B.; Repetto A.; Pasotti C.; Zangaglia R.; Pacchetti C.; Manni R.Ratti, P. -L.; Terzaghi, M.; Minafra, B.; Repetto, A.; Pasotti, C.; Zangaglia, R.; Pacchetti, C.; Manni, R