Gait asymmetry in stroke patients with unilateral spatial neglect.

The recovery of independent gait represents one of the main functional goals of the rehabilitative interventions after stroke but it can be hindered by the presence of unilateral spatial neglect (USN). The aim of the paper is to study if the presence of USN in stroke patients affects lower limb gait parameters between the two body sides, differently from what could be expected by the motor impairment alone, and to explore whether USN is associated to specific gait asymmetry. Thirty-five stroke patients (right or left lesion and ischemic or hemorrhagic etiology) who regained independent gait were assessed for global cognitive functioning and USN. All patients underwent a gait analysis session by using a wearable inertial system, kinematic parameters were computed. Enrolled patients presented altered motion parameters. Stroke patients with USN showed specific asymmetries in the following parameters: stance phase, swing phase, and knee range of motion. No differences in the clinical scores were found as the presence of USN. The presence of USN was associated with a specific form of altered gait symmetry. These findings may help clinicians to develop more tailored rehabilitative training to enhance gait efficacy of patients with motor defects complicated by the presence of selected cognitive impairments. Overview of the experiment setup. The workflow shows: diagnosis of unilateral spatial neglect by the neuropsychologist, sensors placement, gait analysis protocol and evaluation of the gait asymmetry together with the statistically significant features.

Peripheral Neuropathy in Patients Recovering from Severe COVID-19: A Case Series.

Background and Objectives: Neurological manifestations have been reported in a significant proportion of coronavirus disease 2019 (COVID-19) patients. We aimed to evaluate the prevalence and severity of peripheral nervous system (PNS) involvement in a large group of convalescent COVID-19 patients undergoing in-hospital multidisciplinary rehabilitation. Materials and Methods: Convalescent COVID-19 patients admitted to a Pulmonary Rehabilitation Unit were consecutively screened for inclusion within 48 h of discharge from an acute care setting. All included patients underwent electrophysiological examinations. Results: Among 102 enrolled patients (mean age 62.0 years, 82.4% males), PNS electrophysiological alterations were detected in 42.2%. Mononeuropathies exclusively involving the peroneal nerve were observed in 8.8% (n = 9), while multiple mononeuropathies were similarly reported in nine patients (8.8%). A symmetric sensorimotor polyneuropathy was documented in 24.5% of participants (n = 25). A significant difference was found for exercise capacity and pulmonary function in post hoc comparisons between the three study groups. Conclusions: The risk of neuropathy in the convalescent phase of COVID-19 is relevant. This should be considered when planning multidisciplinary rehabilitation strategies.

Positive impact of short-term gait rehabilitation in Parkinson patients: a combined approach based on statistics and machine learning.

Parkinson's disease is the second most common neurodegenerative disorder in the world. Assumed that gait dysfunctions represent a major motor symptom for the pathology, gait analysis can provide clinicians quantitative information about the rehabilitation outcome of patients. In this scenario, wearable inertial systems for gait analysis can be a valid tool to assess the functional recovery of patients in an automatic and quantitative way, helping clinicians in decision making. Aim of the study is to evaluate the impact of the short-term rehabilitation on gait and balance of patients with Parkinson's disease. A cohort of 12 patients with Idiopathic Parkinson's disease performed a gait analysis session instrumented by a wearable inertial system for gait analysis: Opal System, by APDM Inc., with spatial and temporal parameters being analyzed through a statistic and machine learning approach. Six out of fourteen motion parameters exhibited a statistically significant difference between the measurements at admission and at discharge of the patients, while the machine learning analysis confirmed the separability of the two phases in terms of Accuracy and Area under the Receiving Operating Characteristic Curve. The rehabilitation treatment especially improved the motion parameters related to the gait. The study shows the positive impact on the gait of a short-term rehabilitation in patients with Parkinson's disease and the feasibility of the wearable inertial devices, that are increasingly spreading in clinical practice, to quantitatively assess the gait improvement.

Milestones and Timescale of Poststroke Recovery: A Cohort Study.

BACKGROUND: Progressive increase of an aging population in Western countries will result in a growth of stroke prevalence. As many stroke survivors chronically show severe disability, increase in economic, social, and medical burden could be expected in the future. Objective and subjective measures of poststroke recovery are necessary to obtain predictive information, to improve the treatments, and to better allocate resources. AIM: To explore a measure of the temporal dimension of poststroke recovery, to search for predictive association with multiple clinical variables, and to improve tailoring of poststroke treatments. METHOD: In this observational monocentric cohort study, 176 poststroke inpatients at their first cerebrovascular event were consecutively enrolled. A novel measure based on the time needed to reach the main milestones of motor recovery was proposed. Moreover, two commonly used outcome measures, a measure of global functioning (Functional Independence Measure (FIM™)) and a measure of neurological poststroke deficit (Fugl-Meyer scale), were collected for the investigations of possible predictors. RESULTS: The patients showed a substantial increase in Fugl-Meyer and FIM scores during the rehabilitative treatment. The acquisition of three milestones was significantly associated with female sex (autonomous standing), length of stay and Fugl-Meyer initial score (autonomous walking), and Fugl-Meyer initial score (functional arm). These findings provided quantitative data on motor milestone reacquisition in a sample of poststroke patients. It also demonstrated the value of the Fugl-Meyer score in predicting the acquisition of two motor milestones, relevant for daily life activities. CONCLUSION: Systematic recording of the timescale of poststroke recovery showed that motor milestone reacquisition happens, on average and when attainable, in less than 30 days in our sample of patients. The present study underscores the importance of the Fugl-Meyer score as a possible predictor for better improvement in reacquisition times of milestone functional recovery.

Phenomenological models of NaV1.5. A side by side, procedural, hands-on comparison between Hodgkin-Huxley and kinetic formalisms.

Computational models of ion channels represent the building blocks of conductance-based, biologically inspired models of neurons and neural networks. Ion channels are still widely modelled by means of the formalism developed by the seminal work of Hodgkin and Huxley (HH), although the electrophysiological features of the channels are currently known to be better fitted by means of kinetic Markov-type models. The present study is aimed at showing why simplified Markov-type kinetic models are more suitable for ion channels modelling as compared to HH ones, and how a manual optimization process can be rationally carried out for both. Previously published experimental data of an illustrative ion channel (NaV1.5) are exploited to develop a step by step optimization of the two models in close comparison. A conflicting practical limitation is recognized for the HH model, which only supplies one parameter to model two distinct electrophysiological behaviours. In addition, a step by step procedure is provided to correctly optimize the kinetic Markov-type model. Simplified Markov-type kinetic models are currently the best option to closely approximate the known complexity of the macroscopic currents of ion channels. Their optimization can be achieved through a rationally guided procedure, and allows to obtain models with a computational burden that is comparable with HH models one.

A single Markov-type kinetic model accounting for the macroscopic currents of all human voltage-gated sodium channel isoforms.

Modelling ionic channels represents a fundamental step towards developing biologically detailed neuron models. Until recently, the voltage-gated ion channels have been mainly modelled according to the formalism introduced by the seminal works of Hodgkin and Huxley (HH). However, following the continuing achievements in the biophysical and molecular comprehension of these pore-forming transmembrane proteins, the HH formalism turned out to carry limitations and inconsistencies in reproducing the ion-channels electrophysiological behaviour. At the same time, Markov-type kinetic models have been increasingly proven to successfully replicate both the electrophysiological and biophysical features of different ion channels. However, in order to model even the finest non-conducting molecular conformational change, they are often equipped with a considerable number of states and related transitions, which make them computationally heavy and less suitable for implementation in conductance-based neurons and large networks of those. In this purely modelling study we develop a Markov-type kinetic model for all human voltage-gated sodium channels (VGSCs). The model framework is detailed, unifying (i.e., it accounts for all ion-channel isoforms) and computationally efficient (i.e. with a minimal set of states and transitions). The electrophysiological data to be modelled are gathered from previously published studies on whole-cell patch-clamp experiments in mammalian cell lines heterologously expressing the human VGSC subtypes (from NaV1.1 to NaV1.9). By adopting a minimum sequence of states, and using the same state diagram for all the distinct isoforms, the model ensures the lightest computational load when used in neuron models and neural networks of increasing complexity. The transitions between the states are described by original ordinary differential equations, which represent the rate of the state transitions as a function of voltage (i.e., membrane potential). The kinetic model, developed in the NEURON simulation environment, appears to be the simplest and most parsimonious way for a detailed phenomenological description of the human VGSCs electrophysiological behaviour.

A cola-induced hypokalemic rhabdomyolysis with electromyographic evaluation: A case report.

OBJECTIVE: To report a rare case of hypokalemic rhabdomyolysis induced by the heavy and prolonged ingestion of cola-based beverages, and its uneventful recovery after kalemia normalization. METHODS: We report a 38-year-old Caucasian male presented in our emergency room with a recent and progressive weakness of the lower limbs proximal muscles. RESULTS: A dietary history revealed a prolonged ingestion of cola-based beverages. Blood tests showed severe hypokalemia and marked increase in serum creatine phosphokinase. The analysis of cerebrospinal fluid resulted normal. Electromyography was suggestive for a myopathy. The clinical, laboratory and neurophysiological data were evocative for a cola-induced hypokalemic rhabdomyolysis. After kalemia normalization, the improvements of the electromyographic findings paralleled the clinical recovery. CONCLUSION: Chronic consumption of large amount of cola-based soft drinks may result in severe symptomatic hypokalemia, eventually leading in turn to myopathy. To our knowledge, this is the first description of the electromyographic findings of the cola-induced hypokalemic rhabdomyolysis. An early diagnosis and a prompt treatment appear to be crucial for a benign clinical course.

Pisa Syndrome in Parkinson's Disease: Electromyographic Aspects and Implications for Rehabilitation.

Pisa Syndrome (PS) is a real clinical enigma, and its management remains a challenge. In order to improve the knowledge about resting state and during maximal voluntary muscle contraction (MVMC) of the axial muscles, we described the electromyography results of paraspinal muscles, rectus abdominis, external oblique, and quadratus lumborum of both sides of 60 patients. Electromyography was assessed at rest, during MVMC while bending in the opposite direction of the PS and during MVMC while bending in the direction of the PS. The MVMC gave information about the interferential pattern (INT) or subinterferential pattern (sub-INT). We defined asymmetrical activation (AA) when a sub-INT was detected on the muscle on the side opposite to the PS bending and an INT of same muscle in the direction of PS bending. We observed significant AA during MVMC only in the external oblique muscles in 78% of the subjects. Our results of asymmetric ability to generate maximal voluntary force of the external oblique muscles support a central dissynchronisation of axial muscles as a significant contributor for the bending of the spine in erect position. These results could have important implication to physiotherapy and the use of botulinum toxin in the treatment of PS.

Axon-somatic back-propagation in detailed models of spinal alpha motoneurons.

Antidromic action potentials following distal stimulation of motor axons occasionally fail to invade the soma of alpha motoneurons in spinal cord, due to their passing through regions of high non-uniformity. Morphologically detailed conductance-based models of cat spinal alpha motoneurons have been developed, with the aim to reproduce and clarify some aspects of the electrophysiological behavior of the antidromic axon-somatic spike propagation. Fourteen 3D morphologically detailed somata and dendrites of cat spinal alpha motoneurons have been imported from an open-access web-based database of neuronal morphologies, NeuroMorpho.org, and instantiated in neurocomputational models. An axon hillock, an axonal initial segment and a myelinated axon are added to each model. By sweeping the diameter of the axonal initial segment (AIS) and the axon hillock, as well as the maximal conductances of sodium channels at the AIS and at the soma, the developed models are able to show the relationships between different geometric and electrophysiological configurations and the voltage attenuation of the antidromically traveling wave. In particular, a greater than usually admitted sodium conductance at AIS is necessary and sufficient to overcome the dramatic voltage attenuation occurring during antidromic spike propagation both at the myelinated axon-AIS and at the AIS-soma transitions.

The beneficial role of intensive exercise on Parkinson disease progression.

In the last decade, a considerable number of articles has shown that exercise is effective in improving motor performance in Parkinson disease. In particular, recent studies have focused on the efficacy of intensive exercise in achieving optimal results in the rehabilitation of patients with Parkinson disease. The effects of intensive exercise in promoting cell proliferation and neuronal differentiation in animal models are reported in a large cohort of studies, and these neuroplastic effects are probably related to increased expression of a variety of neurotrophic factors. The authors outline the relation between intensive exercises and neuroplastic activity on animal models of Parkinson disease and discuss the clinical results of different intensive strategies on motor performance and disease progression in patients with Parkinson disease.

Ceftriaxone for Alexander's Disease: A Four-Year Follow-Up.

In 2010, we reported the successful clinical outcome related to a 20-month course of intravenous, cyclical ceftriaxone, in a patient with adult-onset Alexander's disease. We now provide evidence that the progression of the patient's signs/symptoms was halted and reversed with a 4-year-long extension of the trial.The patient's clinical signs/symptoms were evaluated before the start and every 6 months for 6 years. For the early 2 years, without therapy, and for the following 4 years, after intravenous ceftriaxone 2 g daily, for 3 weeks monthly during the initial 4 months, then for 15 days monthly.Gait ataxia and dysarthria were assessed clinically on a 0 to 4 scale. Palatal myoclonus and nystagmus/oscillopsia were monitored by videotape and a self-evaluation scale. The degree of disability, measured by a modified Rankin scale, and the brain MRI were periodically evaluated.Before ceftriaxone therapy, in a 2-year period, gait ataxia and dysarthria worsened from mild to marked, palatal myoclonus spread from the soft palate to lower facial muscles, and the patient complained of oscillopsia. After 4 years of ceftriaxone therapy, gait ataxia and dysarthria improved, from marked to mild at clinical rating scales. The palatal myoclonus was undetectable; the patient did not complained of oscillopsia and declared a progressively better quality of life. Ceftriaxone was safe.This case report provides Class IV evidence that intravenous cycles of ceftriaxone may halt and/or reverse the progression of neurodegeneration in patients with adult-onset Alexander's disease and may significantly improve their quality of life.

Rehabilitation improves dyskinesias in Parkinsonian patients: a pilot study comparing two different rehabilitative treatments.

GOAL AND OBJECTIVES: The present study was devised: (a) to test whether an intensive (60 hours in 4 weeks) multidisciplinary rehabilitation treatment (involving physiotherapy, exercises to improve gait and balance using treadmill and stabilometric platform, occupational therapy) for Parkinsonian patients is effective in improving dyskinesia and motor performance compared to a control group undergoing a non-intensive non multidisciplinary rehabilitation treatment (30 hours in 4 weeks involving physiotherapy only); and (b) to verify whether rehabilitation may lead to a reduction in levodopa dosage. MATERIAL AND METHODS: Forty Parkinsonian patients suffering from dyskinesias were admitted to study: 20 for an intensive multidisciplinary (Group1) and 20 for a non-intensive non multidisciplinary rehabilitation treatment (Group2). The rating scales used for the clinical evaluation were: Unified Parkinson's Disease Rating Scales (UPDRS) II, III, IV, Parkinson's disease disability scale (PDDS), Abnormal Involuntary Movement Scale (AIMS). RESULTS: All outcome measurements improved in both groups of patients, but patients Group1 presented better results: UPDRS II was reduced by 33% in Group1 and by 22% in Group2, UPDRS III 29% vs. 22%, UPDRS IV 74% vs. 10%, PDDS 18% vs. 12%, and AIMS 71% vs. 8%. A different behaviour was observed for levodopa dosage at baseline and after treatment: dosage decreased by an average value of 210 mg (p< 0.0001) in Group1 and was virtually unchanged (30 mg reduction, p=0.08) in Group2. CONCLUSION: Our findings suggest that a rehabilitation protocol should be considered as a valid non-invasive therapeutic support for patients who show dyskinesias and that there are better results when the treatment is intensive.

Beneficial effects of curcumin on GFAP filament organization and down-regulation of GFAP expression in an in vitro model of Alexander disease.

Heterozygous mutations of the GFAP gene are responsible for Alexander disease, a neurodegenerative disorder characterized by intracytoplasmic Rosenthal fibers (RFs) in dystrophic astrocytes. In vivo and in vitro models have shown co-localization of mutant GFAP proteins with the small heat shock proteins (sHSPs) HSP27 and alphaB-crystallin, ubiquitin and proteasome components. Results reported by several recent studies agree on ascribing an altered cytoskeletal pattern to mutant GFAP proteins, an effect which induces mutant proteins accumulation, leading to impaired proteasome function and autophagy induction. On the basis of the protective role shown by both these small heat shock proteins (sHSPs), and on the already well established neuroprotective effects of curcumin in several diseases, we have investigated the effects of this compound in an in vitro model of Alexander disease, consisting in U251-MG astrocytoma cells transiently transfected with a construct encoding for GFAP carrying the p.R239C mutation in frame with the reporter green fluorescent protein (GFP). In particular, depending on the dose used, we have observed that curcumin is able to induce both HSP27 and alphaB-crystallin, to reduce expression of both RNA and protein of endogenous GFAP, to induce autophagy and, finally, to rescue the filamentous organization of the GFAP mutant protein, thus suggesting a role of this spice in counteracting the pathogenic effects of GFAP mutations.

Effectiveness of intensive inpatient rehabilitation treatment on disease progression in parkinsonian patients: a randomized controlled trial with 1-year follow-up.

BACKGROUND: Rehabilitation treatments have acute beneficial effects in Parkinson's disease (PD) patients, but whether the effects persist over time is unclear. OBJECTIVE: To assess whether an intensive rehabilitation treatment (IRT) is effective in improving motor performance compared with a control group in a 12-month follow-up, to investigate whether a second cycle administered after 1 year has the same efficacy as the first treatment, and to determine whether IRT reduces the need for increasing levodopa dosage. METHODS: A total of 50 PD patients were randomly assigned to 2 groups; 25 participants had 4 weeks of inpatient physical therapy that included treadmill and stabilometric platform training. At discharge, these patients were invited to continue doing the learned exercises. After 12 months, the same treatment was repeated. The control group of 25 patients received only pharmacological treatment and was invited to practice generic physical exercise at home. The rating scales used for the clinical evaluation were the Unified Parkinson's Disease Rating Scale Sections II and III (UPDRS II and III) and total (UPDRS tot). RESULTS: The authors found that the beneficial effects of IRT persisted over time. A second rehabilitation cycle administered after 1 year was as effective as the first treatment. At the end of the study, daily medication dosage was reduced in treated patients, whereas it was significantly increased in control patients. CONCLUSION: These findings suggest that the natural worsening of symptoms associated with PD can be effectively counteracted by a properly designed IRT.

The clinical spectrum of late-onset Alexander disease: a systematic literature review.

Following the discovery of glial fibrillary acidic protein (GFAP) mutations as the causative factor of Alexander disease (AxD), new case reports have recently increased, prompting a more detailed comprehension of the clinical features of the three disease subtypes (infantile, juvenile and adult). While the clinical pattern of the infantile form has been substantially confirmed, the late-onset subtypes (i.e., juvenile and adult), once considered rare manifestations of AxD, have displayed a wider clinical spectrum. Our aim was to evaluate the clinical phenotype of the adult and juvenile forms by reviewing the previously reported cases. Data were collected from previously published reports on 112 subjects affected by neuropathologically or genetically proven adult and juvenile Alexander disease. Although the late-onset forms of AxD show a wide clinical variability, a common pattern emerges from comparing previously reported cases, characterized by pseudo-bulbar signs, ataxia, and spasticity, associated with atrophy of the medulla and upper cervical cord on neuroimaging. Late-onset AxD cases can no longer be considered as rare manifestations of the disease. The clinical pattern usually reflects the topographic localization of the lesions, with adult cases displaying a predominant infratentorial localization of the lesions. Juvenile cases show clinical and radiological features which are intermediate between adult and infantile forms.