Current and emerging treatments for amyotrophic lateral sclerosis

Stefano Zoccolella1, Andrea Santamato2, Paolo Lamberti31Azienda Ospedaliero-UniversitariaOspedali Riuniti, Department of Medical and Neurological Sciences, Clinic of Nervous System Diseases, University of Foggia, Italy; 2Department of Physical Medicine and Rehabilitation, University of Foggia, OORR, Italy; 3Department of Neurology and Psychiatry, University of Bari, ItalyBackground: Amyotrophic lateral sclerosis (ALS) is a relatively rare neurodegenerative disorder of both upper and lower motoneurons. Currently, the management of ALS is essentially symptoms-based, and riluzole, an antiglutamatergic agent, is the only drug for the treatment of ALS approved by the food and drug administration.Objective: We reviewed current literature concerning emerging treatments for amyotrophic lateral sclerosis.Methods: A Medline literature search was performed to identify all studies on ALS treatment published from January 1st, 1986 through August 31st, 2009. We selected papers concerning only disease-modifying therapy.Results: Forty-eight compounds were identified and reviewed in this study.Conclusions: Riluzole is the only compound that demonstrated a beneficial effect on ALS patients, but with only modest increase in survival. Although several drugs showed effective results in the animal models for ALS, none of them significantly prolonged survival or improved quality of life of ALS patients. Several factors have been implicated in explaining the predominantly negative results of numerous randomized clinical trials in ALS, including methodological problems in the use of animal-drug screening, the lack of assessment of pharmacokinetic profile of the drugs, and methodological pitfalls of clinical trials in ALS patients.Keywords: amyotrophic lateral sclerosis, therapy, drug, surviva

The role of the rehabilitation in subjects with Progressive Supranuclear Palsy: a narrative review

Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative disorder due to the deposition of abnormal proteins in neurons of the basal ganglia that limit motor ability producing disability and reduced quality of life. So far, no pharmacologic therapy has been developed and the treatment remains symptomatic. The aim of the present study was to investigate systematically literature, and to determine the types and effects of rehabilitative interventions. A search of all studies was conducted in MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials, CINAHL and EMBASE. Twelve studies were individuated including 6 case reports, 3 case series, one case control, one quasi-RT crossover study and one RCT, with 88 patients investigated overall. Rehabilitative interventions varied in type, number, frequency and duration of sessions. The most commonly used clinical measures were Progressive Supranuclear Palsy-Rating Scale (PSP-RS) and Unified Parkinson's Disease Rating Scale (UPDRS). Physical exercises were the main rehabilitative strategy but were associated with other interventions and rehabilitative devices, in particular treadmill and robot-assisted gait training. All studies showed an improvement of balance and gait impairment with a reduction of falls after rehabilitation treatment. Due to poor methodological quality and the variability of rehabilitative approach with different and variable strategies, there was no evidence of the effectiveness of a specific rehabilitation intervention in PSP. Despite this finding, rehabilitation might improve balance and gait, thereby reducing falls in PSP subjects

Sensor-Based Rehabilitation in Neurological Diseases: A Bibliometric Analysis of Research Trends

Background: As the field of sensor-based rehabilitation continues to expand, it is important to gain a comprehensive understanding of its current research landscape. This study aimed to conduct a bibliometric analysis to identify the most influential authors, institutions, journals, and research areas in this field. Methods: A search of the Web of Science Core Collection was performed using keywords related to sensor-based rehabilitation in neurological diseases. The search results were analyzed with CiteSpace software using bibliometric techniques, including co-authorship analysis, citation analysis, and keyword co-occurrence analysis. Results: Between 2002 and 2022, 1103 papers were published on the topic, with slow growth from 2002 to 2017, followed by a rapid increase from 2018 to 2022. The United States was the most active country, while the Swiss Federal Institute of Technology had the highest number of publications among institutions. Sensors published the most papers. The top keywords included rehabilitation, stroke, and recovery. The clusters of keywords comprised machine learning, specific neurological conditions, and sensor-based rehabilitation technologies. Conclusions: This study provides a comprehensive overview of the current state of sensor-based rehabilitation research in neurological diseases, highlighting the most influential authors, journals, and research themes. The findings can help researchers and practitioners to identify emerging trends and opportunities for collaboration and can inform the development of future research directions in this field

Hyperhomocysteinemia in L-dopa treated patients with Parkinson's disease: potential implications in cognitive dysfunction and dementia?

Abstract: Background: Hyperhomocysteinemia has been associated with cognitive dysfunction and dementia. The incidence of dementia in Parkinson’s Disease (PD) patients is higher than in the general population and plasma Homocysteine concentrations are increased in L-dopa treated PD patients. Objective: We evaluated the possible correlations between L-Dopa related hyperhomocysteinemia and cognitive dysfunction in PD. Methods: A Medline literature search was performed to identify all published studies on Homocysteine and cognitive dysfunction and dementia during the course of PD from 1966 to 31/03/2010. Results: Sixteen studies were found for review; ten studies focused on homocysteine and cognitive dysfunction in PD patients, five on homocysteine and PD dementia and two on homocysteine and markers of neurodegeneration in PD. The design of the study was retrospective in 14 studies, while 2 had a prospective design, with a variable follow-up period (from 24-weeks to 2 years). In most of the studies plasma homocysteine levels significantly correlated with cognitive functions, dementia and markers of neurodegeneration in PD patients. However, some studies did not confirm these findings. Several factors may concur to explain these partially conflicting results, including the retrospective design of the studies, their small sample size, their high percentage of excluded patients, and the use of a wide range of neuropsychological tasks in assessment of cognitive dysfunctions across the available studies. Conclusions: Available data seem to indicate a potential role of L-dopa related hyperhomocysteinemia on cognitive impairment and dementia during the course of PD

Alternative pharmacological treatment options for agitation in Alzheimer's disease

In patients with dementia and Alzheimer's disease (AD), treatment of neuropsychiatric symptoms (NPS) is a major concern in the management of these devastating diseases. Among NPS in AD, agitation and aggression are common with earlier institutionalization, increased morbidity and mortality, and greater caregiver burden. Pharmacological treatments for AD-related agitation, specifically off-label use of atypical antipsychotics, showed only modest improvements, with increased side-effect burden and risk of mortality. Non-pharmacological treatment approaches have become the preferred firstline option. However, when such treatments fail, pharmacological options are often used. Therefore, there is an urgent need to identify effective and safe pharmacological treatments for agitation/aggression in AD and dementia. Unfortunately, progresses have been slow, with a small number of methodologically heterogeneous randomized controlled trials (RCTs), with disappointing results. However, evidence coming from recently completed RCTs on novel or repositioned drugs (mibampator, dextromethorphan/ quinidine, cannabinoids, and citalopram) showed some promise in treating agitation in AD, but still with safety concerns. Further evidence will come from ongoing Phase II and III trials on promising novel drugs for treating these distressing symptoms in patients with AD and dementia

Anatomical landmarks for ultrasound‐guided rectus femoris diagnostic nerve block in post‐stroke spasticity

Introduction/Purpose To determine the location of the rectus femoris (RF) motor branch nerve, as well as its coordinates with reference to anatomical and ultrasound landmarks. Methods Thirty chronic stroke patients with stiff knee gait (SKG) and RF hyperactivity were included. The motor nerve branch to the RF muscle was identified medially to the vertical line from anterior superior iliac spine and the midpoint of the superior margin of the patella (line AP) and vertically to the horizontal line from the femoral pulse and its intersection point with the line AP (line F). The point of the motor branch (M) was located with ultrasound, and nerve depth and subcutaneous tissue thickness (ST) were calculated. Results The coordinates of the motor branch to the RF were 2.82 (0.47) cm medially to the line AP and 4.61 (0.83) cm vertically to the line F. Nerve depth and subcutaneous tissue thickness were 2.71 (0.62) cm and 1.12 (0.75) cm, respectively. Conclusion The use of specific coordinates may increase clinicians' confidence when performing RF motor nerve block. This could lead to better decision-making when assessing SKG in chronic stroke patients

Adjunctive treatment and BoNT-A for post-stroke spasticity: are we really focusing on the patient-centered goals?

[no abstract available

Is the outcome of diagnostic nerve block related to spastic muscle echo intensity? A retrospective observational study on patients with spastic equinovarus foot

Objective: To investigate the relationship between spastic calf muscles echo intensity and outcome of tibial nerve motor branches selective block in patients with spastic equinovarus foot. Design: Retrospective observational study. Patients: Forty-eight patients with spastic equinovarus foot. Methods: Each patient was given selective, diagnostic nerve block (lidocaine 2% perineural injection) of the tibial nerve motor branches. All patients were evaluated before and after block. Outcomes: spastic calf muscles echo intensity measured with the Heckmatt scale; affected ankle dorsiflexion passive range of motion; calf muscles spasticity measured with the modified Ashworth scale and the Tardieu scale (grade and angle). Results:  As to the outcome of tibial nerve selective diagnostic block (difference between pre- and post-block condition), the Spearman correlation showed a significant inverse association of the spastic calf muscles echo intensity with the affected ankle dorsiflexion passive range of motion (P=0.045