The Effect of Upright Stance and Vision on a Cognitive Task in Elderly Subjects and Patients with Parkinson's Disease.

Standing compared to sitting enhances cognitive performance in healthy subjects. The effect of stance on cognitive performance has been addressed here in patients with Parkinson's disease (PwPD). We hypothesized that a simple cognitive task would be less enhanced in PwPD by standing with respect to sitting, because of a larger cognitive effort for maintenance of standing posture than in healthy subjects. We recruited 40 subjects (20 PwPD and 20 age-matched healthy subjects, HE). Each participant performed an arithmetic task (backward counting aloud by 7) in two postural states, sitting and standing, with eyes open (EO) and with eyes closed (EC). All trials lasted 60 s and were randomized across subjects and conditions. The number of correct subtractions per trial was an index of counting efficiency and the ratio of correct subtractions to total subtractions was an index of accuracy. All conditions collapsed, the efficiency of the cognitive task was significantly lower in PwPD than HE, whilst accuracy was affected to a lower extent. Efficiency significantly improved from sitting to standing in HE under both visual conditions whilst only with EO in PwPD. Accuracy was not affected by posture or vision in either group. We suggest that standing, compared to sitting, increases arousal, thus improving the cognitive performance in HE. Conversely, in PwPD this improvement was present only with vision, possibly due to their greater balance impairment with EC consuming an excess of attentional resources. These findings have implications for balance control and the risk of falling in PwPD in the absence of visual cues.

Metachromatic leukodystrophy: A single-center longitudinal study of 45 patients.

In this study, we characterize the natural course of metachromatic leukodystrophy (MLD), explore intra/inter group differences, and identify biomarkers to monitor disease progression. This is a longitudinal observational study. Genotype and characteristics at disease onset were recorded. Time-to-event analyses were performed to assess time to major disease-related milestones in different subgroups. Longitudinal trajectories of nerve conduction velocities (NCV), brain MRI score, and brainstem auditory evoked responses (BAERs) were described. We recruited 22 late-infantile, 14 early-juvenile, 5 late-juvenile, and 4 adult MLD patients. Thirty-four were prospectively evaluated (median FU time 43 months). In late-infantile patients, the attainment of independent walking was associated with a later age at dysphagia. In early-juvenile, the presence of isolated cognitive impairment at onset was not a favorable prognostic factor. Late-infantile and early-juvenile subjects showed similar rapid loss of ambulation and onset of seizures, but late-infantile displayed earlier loss of trunk control, dysphagia, and death. We found significant differences in all major disease-related milestones (except death) between early-juvenile and late-juvenile patients. Late-juvenile and adult patients both presented with a predominant cognitive impairment, mild/no peripheral neuropathy, lower brain MRI score at plateau compared to LI/EJ, and later cerebellar involvement. NCV and BAER were consistently severely abnormal in late-infantile but not in older subjects, in whom both NCV and BAER were variably affected, with no deterioration over time in some cases. This study clarifies intra/inter group differences between MLD subtypes and provides additional indications regarding reliable clinical and instrumental tools to monitor disease progression and to serve as areference to evaluate the efficacy of future therapeutic interventions inthe different MLD variants.

Cranial nerves impairment in post-acute oropharyngeal dysphagia after COVID-19.

BACKGROUND: According to literature, after COVID-19, patients may require rehabilitation care because of different degrees of physical impairments. Neurologic disorders are often described but no specific data about postacute cranial nerves involvement and possible correlation with dysphagia development are yet available. CASE REPORT: The patient is a 69-year-old man who presented acquired weakness and dysphagia with clinical cranial nerves impairment of lingual, IX, X and XII after SARS-CoV-2 infection, without electrophysiological alterations. He underwent rehabilitation program for two months, with slow recovery. However, at discharge residual hypoglossal nerve deficit sign was present. CLINICAL REHABILITATION IMPACT: This single case expands knowledge about clinical picture after SARS-CoV-2 disease. Is important to notice that cranial, particularly bulbar nerves could be involved as late complications. Thus, we discuss about risk factors, the nature of the damage and the impact in dysphagia pathophysiology and recovery. If supported by further studies, this case may help to understand dysphagia features in these patients.

Cognitive performance during gait is worsened by overground but enhanced by treadmill walking.

PURPOSE: Walking is an attention-demanding task that affects and is affected by cognitive performance. Since treadmill walking (TW) assists gait automaticity, we have hypothesized that TW affects cognitive performance to a smaller extent than overground walking (OW). METHODS: Thirty young adults were recruited. Each subject walked overground over a 20-meter straight hallway at three different speeds (slow, normal and fast). Each task was repeated 3 times under Single Task (OW-ST) and Dual Task (OW-DT) condition, in a randomized sequence. DT was a serial subtraction by 7 starting from a different number (> 100) in each trial. Afterwards, each subject walked on the treadmill at the same three speeds as during OW-ST, while performing the dual task (TW-DT). The correct cognitive response (CCR), calculated from the number of correct responses and mistakes, was compared between rest, OW-DT and TW-DT. Dual-task cost (DTC) was calculated for speed and for CCR. RESULTS: Backward counting diminished normal and fast OW-DT speed by about 15 %. Slow OW-DT speed was not significantly reduced. In turn, OW affected the cognitive performance. DTC for speed during OW-DT increased during normal and fast speed. CCR significantly decreased, more at slower OW-DT speed. Conversely, CCR was not worsened by TW-DT. CCR did not decline at slow TW-DT speed and improved significantly from slow and normal to fast speeds. DTC for CCR resulted smaller in TW-DT than OW-DT. CONCLUSIONS: Decline in the cognitive performance during OW-DT is more prominent at slow speed, in keeping with higher demand of attentional resources for this unusual locomotor behaviour. Conversely, motorized TW improves the cognitive performance likely because it reduces the attentional cost of walking. Gait training by TW might improve automaticity in patients with movement disorders.

Lower Tinetti scores can support an early diagnosis of spatial neglect in post-stroke patients.

BACKGROUND: Neglect represents a severe complication of stroke, which impairs patients' daily activities. An early diagnosis of neglect is fundamental for management decisions. AIM: The aim of this study is to evaluate the usefulness of the Tinetti Test as an outcome of spatial neglect in post-stroke patients. DESIGN: Observational retrospective data analysis. SETTING: Rehabilitation Hospital. POPULATION: Cohort of post-stroke adults admitted in our Rehabilitation Unit. METHODS: One hundred and sixty stroke patients were evaluated between the 1st of January 2015 and the 31st of December 2016 at our Department. Eighty-nine inpatients matched the inclusion criteria. Their scores of the Tinetti Test for balance condition and gait function were compared with Bells Test and line bisection task for spatial neglect. Global independence activity was also assessed using Barthel Index and global cognitive functioning by means of the Mini-Mental State Examination. RESULTS: Twenty-two patients between the 89 patients included in this study were affected by spatial neglect at admission. A high statistical significant correlation was observed between lower Tinetti scores and neglect presence (mean Tinetti Score: 2.36 neglect; 7.82 non-neglect; P<0.001). CONCLUSIONS: The Tinetti Test is a well-established assessment scale to measure balance ability and gait function in post-stroke patients. Results from this study suggest that Tinetti Test may be considered as an early ecological screening tool for the diagnosis of neglect in post-stroke patients. CLINICAL REHABILITATION IMPACT: The alternative use of the Tinetti Test for the diagnosis of spatial neglect.

Gene therapy for lysosomal storage disorders: recent advances for metachromatic leukodystrophy and mucopolysaccaridosis I.

Lysosomal storage diseases (LSDs) are rare inherited metabolic disorders characterized by a dysfunction in lysosomes, leading to waste material accumulation and severe organ damage. Enzyme replacement therapy (ERT) and haematopoietic stem cell transplant (HSCT) have been exploited as potential treatments for LSDs but pre-clinical and clinical studies have shown in some cases limited efficacy. Intravenous ERT is able to control the damage of visceral organs but cannot prevent nervous impairment. Depending on the disease type, HSCT has important limitations when performed for early variants, unless treatment occurs before disease onset. In the attempt to overcome these issues, gene therapy has been proposed as a valuable therapeutic option, either ex vivo, with target cells genetically modified in vitro, or in vivo, by inserting the genetic material with systemic or intra-parenchymal, in situ administration. In particular, the use of autologous haematopoietic stem cells (HSC) transduced with a viral vector containing a healthy copy of the mutated gene would allow supra-normal production of the defective enzyme and cross correction of target cells in multiple tissues, including the central nervous system. This review will provide an overview of the most recent scientific advances in HSC-based gene therapy approaches for the treatment of LSDs with particular focus on metachromatic leukodystrophy (MLD) and mucopolysaccharidosis type I (MPS-I).