Acute and Chronic Effect of Acoustic and Visual Cues on Gait Training in Parkinson’s Disease: A Randomized, Controlled Study

In this randomized controlled study we analyse and compare the acute and chronic effects of visual and acoustic cues on gait performance in Parkinson’s Disease (PD). We enrolled 46 patients with idiopathic PD who were assigned to 3 different modalities of gait training: (1) use of acoustic cues, (2) use of visual cues, or (3) overground training without cues. All patients were tested with kinematic analysis of gait at baseline (T0), at the end of the 4-week rehabilitation programme (T1), and 3 months later (T2). Regarding the acute effect, acoustic cues increased stride length and stride duration, while visual cues reduced the number of strides and normalized the stride/stance distribution but also reduced gait speed. As regards the chronic effect of cues, we recorded an improvement in some gait parameters in all 3 groups of patients: all 3 types of training improved gait speed; visual cues also normalized the stance/swing ratio, acoustic cues reduced the number of strides and increased stride length, and overground training improved stride length. The changes were not retained at T2 in any of the experimental groups. Our findings support and characterize the usefulness of cueing strategies in the rehabilitation of gait in PD

Electrode displacement after intracerebral hematoma as a complication of a deep brain stimulation procedure

Domenico Servello1, Marco Sassi1, Stefano Bastianello2, Guy Umberto Poloni2, Francesca Mancini3, Claudio Pacchetti31Functional Neurosurgery Unit, Istituto di Ricovero e Cura a Carattere Scientifico Galeazzi, Milan, Italy; 2Neuroradiology Unit; 3Parkinson Disease and Movement Disorder Unit, Istituto di Ricovero e Cura a Carattere Scientifico Mondino, Institute of Neurology, Pavia, Italy Objectives: Deep brain stimulation (DBS) is nowadays considered a safe and effective procedure for various movement disorders in which conservative treatments have failed to show significant therapeutic results. One of the most common complications of definitive electrode positioning is intraparenchymal hemorrhage.Materials and methods: Authors report the case of a 55-year-old female patient treated for Parkinson’s disease in which intraparenchymal hemorrhage developed after DBS procedure, leading to significant (about 8 mm at the neuroradiological controls) displacement of an otherwise correctly positioned DBS electrode.Results: After conservative management, the hematoma spontaneously resolved. Late neuroradiological controls documented correct, symmetrically positioned electrodes, comparable to the immediate postoperative controls.Conclusions: Six months follow-up endpoint results of the DBS treatment were considered satisfying by an independent neurologist, with modest residual neurological deficits, demonstrating that re-positioning of the electrode was unnecessary in this rare complication.Keywords: deep brain stimulation, electrodes, outcomes, implant, case repor

Clinical and Cognitive Features of Idiopathic Normal Pressure Hydrocephalus

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by dilated cerebral ventricles with progressive impaired gait, cognition, and urinary control. Firstly described in 1965 by Hakim and Adam, it remains largely under-diagnosed. The diagnosis is based on clinical and imaging (CT or MRI) investigations; a timely diagnosis and cerebrospinal fluid (CSF) shunt surgery has reported to be beneficial in 60 up to 80% of the cases

Ethical safety of deep brain stimulation: A study on moral decision-making in Parkinson's disease

INTRODUCTION: The possibility that deep brain stimulation (DBS) in Parkinson's disease (PD) alters patients' decisions and actions, even temporarily, raises important clinical, ethical and legal questions. Abnormal moral decision-making can lead to ethical rules violations. Previous experiments demonstrated the subthalamic (STN) activation during moral decision-making. Here we aim to study whether STN DBS can affect moral decision-making in PD patients. METHODS: Eleven patients with PD and bilateral STN DBS implant performed a computerized moral task in ON and OFF stimulation conditions. A control group of PD patients without DBS implant performed the same experimental protocol. All patients underwent motor, cognitive and psychological assessments. RESULTS: STN stimulation was not able to modify neither reaction times nor responses to moral task both when we compared the ON and the OFF state in the same patient (reaction times, p = .416) and when we compared DBS patients with those treated only with the best medical treatment (reaction times: p = .408, responses: p = .776). CONCLUSIONS: Moral judgment is the result of a complex process, requiring cognitive executive functions, problem-solving, anticipations of consequences of an action, conflict processing, emotional evaluation of context and of possible outcomes, and involving different brain areas and neural circuits. Our data show that STN DBS leaves unaffected moral decisions thus implying relevant clinical and ethical implications for DBS consequences on patients' behavior, on decision-making and on judgment ability. In conclusion, the technique can be considered safe on moral behavior

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

Body Weight Support Combined With Treadmill in the Rehabilitation of Parkinsonian Gait: A Review of Literature and New Data From a Controlled Study

Background: Gait disorders represent disabling symptoms in Parkinson's Disease (PD). The effectiveness of rehabilitation treatment with Body Weight Support Treadmill Training (BWSTT) has been demonstrated in patients with stroke and spinal cord injuries, but limited data is available in PD.Aims: The aim of the study is to investigate the efficacy of BWSTT in the rehabilitation of gait in PD patients.Methods: Thirty-six PD inpatients were enrolled and performed rehabilitation treatment for 4-weeks, with daily sessions. Subjects were randomly divided into two groups: both groups underwent daily 40-min sessions of traditional physiokinesitherapy followed by 20-min sessions of overground gait training (Control group) or BWSTT (BWSTT group). The efficacy of BWSTT was evaluated with clinical scales and Computerized Gait Analysis (CGA). Patients were tested at baseline (T0) and at the end of the 4-weeks rehabilitation period (T1).Results: Both BWSTT and Control groups experienced a significant improvement in clinical scales as FIM and UPDRS and in gait parameters for both interventions. Even if we failed to detect any statistically significant differences between groups in the different clinical and gait parameters, the intragroup analysis captured a specific pattern of qualitative improvement associated to cadence and stride duration for the BWSTT group and to the swing/stance ratio for the Control group. Four patients with chronic pain or anxious symptoms did not tolerate BWSTT.Conclusions: BWSTT and traditional rehabilitation treatment are both effective in improving clinical motor functions and kinematic gait parameters. BWSTT may represent an option in PD patients with specific symptoms that limit traditional overground gait training, e.g., severe postural instability, balance disorder, orthostatic hypotension. BWSTT is generally well-tolerated, though caution is needed in subjects with chronic pain or with anxious symptoms.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT0381540

PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability

The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T&gt;G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C&gt;A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.</p