Rehabilitation interventions for glioma patients: a mini-review.

Glioma is a group of tumors that originate from glial cells within the central nervous system and comprise 27% of all tumors and 80% of malignant tumors. With remarkable progress in surgical practices, chemotherapy, and radiation therapy, patients with glioma are experiencing greater survival times, which means they need more rehabilitative care. In fact, people with this condition may experience a variety of symptoms that can affect their functions and drastically reduce their quality of life. In fact, patients suffering from glioma has a distinctive symptom complex highlighting the requirement for customized care. Growing evidence shows that rehabilitation therapy can improve the functional prognosis and quality of life of glioma patients. However, there is limited evidence of the success of rehabilitation protocols designed specifically for individuals with glioma. It is essential to determine the most comprehensive rehabilitation programs as well as the sufficient resources, dosage, and duration. The goal of this mini-review was to classify and map rehabilitation interventions used to treat multiple disabling sequalae in individuals affected by glioma. We aim to provide a comprehensive overview of the rehabilitation protocols used for this population, so that clinicians have a guide to support treatment and an inspiration for further research. This document is intended to be a reference point for professionals involved in the management of adult patients with gliomas. Further exploration is needed to form improved care models for recognizing and addressing functional restrictions in this population.

Clinical efficacy of botulinum toxin type A in patients with traumatic brain injury, spinal cord injury, or multiple sclerosis: An observational longitudinal study.

Botulinum toxin type A (BoNT-A) is the treatment of choice for focal spasticity, with a concomitant effect on pain reduction and improvement of quality of life (QoL). Current evidence of its efficacy is based mainly on post stroke spasticity. This study aims to clarify the role of BoNT-A in the context of non-stroke spasticity (NSS). We enrolled 86 patients affected by multiple sclerosis, spinal cord injury, and traumatic brain injury with clinical indication to perform BoNT-A treatment. Subjects were evaluated before injection and after 1, 3, and 6 months. At every visit, spasticity severity using the modified Ashworth scale, pain using the numeric rating scale, QoL using the Euro Qol Group EQ-5D-5L, and the perceived treatment effect using the Global Assessment of Efficacy scale were recorded. In our population BoNT-A demonstrated to have a significant effect in improving all the outcome variables, with different effect persistence over time in relation to the diagnosis and the number of treated sites. Our results support BoNT-A as a modifier of the disability condition and suggest its implementation in the treatment of NSS, delivering a possible starting point to generate diagnosis-specific follow-up programs. Clinical trial identifier: NCT04673240.

Balance Rehabilitation through Robot-Assisted Gait Training in Post-Stroke Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Balance impairment is a common disability in post-stroke survivors, leading to reduced mobility and increased fall risk. Robotic gait training (RAGT) is largely used, along with traditional training. There is, however, no strong evidence about RAGT superiority, especially on balance. This study aims to determine RAGT efficacy on balance of post-stroke survivors. METHODS: PubMed, Cochrane Library, and PeDRO databases were investigated. Randomized clinical trials evaluating RAGT efficacy on post-stroke survivor balance with Berg Balance Scale (BBS) or Timed Up and Go test (TUG) were searched. Meta-regression analyses were performed, considering weekly sessions, single-session duration, and robotic device used. RESULTS: A total of 18 trials have been included. BBS pre-post treatment mean difference is higher in RAGT-treated patients, with a pMD of 2.17 (95% CI 0.79; 3.55). TUG pre-post mean difference is in favor of RAGT, but not statistically, with a pMD of -0.62 (95%CI - 3.66; 2.43). Meta-regression analyses showed no relevant association, except for TUG and treatment duration (ß = -1.019, 95% CI - 1.827; -0.210, p-value = 0.0135). CONCLUSIONS: RAGT efficacy is equal to traditional therapy, while the combination of the two seems to lead to better outcomes than each individually performed. Robot-assisted balance training should be the focus of experimentation in the following years, given the great results in the first available trials. Given the massive heterogeneity of included patients, trials with more strict inclusion criteria (especially time from stroke) must be performed to finally define if and when RAGT is superior to traditional therapy.

Reasons and Determinants of BoNT-A Treatment Discontinuation in Patients Living with Spasticity: A 10-Year Retrospective Analysis.

BACKGROUND: The present study aimed to evaluate the reasons and determinants of BoNT-A discontinuation in patients with stroke, multiple sclerosis, spinal cord injury, and traumatic brain injury. METHODS: It is a retrospective study of 56 discontinuer patients treated with botulinum toxin between January 2011 and December 2021. Discontinuation rates and their predictors were estimated using Kaplan-Meier, Log rank test, and Cox's regression method of analyses. RESULTS: The mean age was 56.54 years, 53.57% were affected by post-stroke spasticity, 17.86% by spinal cord injury, 12.5% and 16.07% by traumatic brain injury and multiple sclerosis, respectively. The median discontinuation time was 5 months. The main reason for discontinuation were logistic problems (37%) and orthopedic surgeries or intrathecal baclofen (27%). Discontinuers were more likely to have severe spasticity (R = 1.785), have no pain (HR = 1.320), no access to rehabilitation services (HR = 1.402), and have cognitive impairment (HR = 1.403). CONCLUSIONS: The main reasons for discontinuation are related to logistic issues (due to distance or the absence of an adequate caregiver) and surgical interventions for spasticity, including intrathecal baclofen. It is crucial to identify possible predictors of discontinuation to improve the effectiveness of a multidisciplinary management. The study confirms the crucial role of rehabilitation and caregivers in achieving better long-term outcomes.

Ischemic Stroke in a 29-Year-Old Patient with COVID-19: A Case Report.

Increasing evidence reports a greater incidence of stroke among patients with Coronavirus disease 2019 (COVID-19) than the non-COVID-19 population and suggests that SARS-CoV-2 infection represents a risk factor for thromboembolic and acute ischemic stroke. Elderly people have higher risk factors associated with acute ischemic stroke or embolization vascular events, and advanced age is strongly associated with severe COVID-19 and death. We reported, instead, a case of an ischemic stroke in a young woman during her hospitalization for COVID-19-related pneumonia. A 29-year-old woman presented to the emergency department of our institution with progressive respiratory distress associated with a 2-day history of fever, nausea, and vomiting. The patient was transferred to the intensive care unit (ICU) where she underwent a tracheostomy for mechanical ventilation due to her severe clinical condition and her very low arterial partial pressure of oxygen. The nasopharyngeal swab test confirmed SARS-CoV-2 infection. Laboratory tests showed neutrophilic leucocytosis, a prolonged prothrombin time, and elevated D-dimer and fibrinogen levels. After 18 days, during her stay in the ICU after suspension of the medications used for sedation, left hemiplegia was reported. Central facial palsy on the left side, dysarthria, and facial drop were present, with complete paralysis of the ipsilateral upper and lower limbs. Computed tomography (CT) of the head and magnetic resonance imaging of the brain confirmed the presence of lesions in the right hemisphere affecting the territories of the anterior and middle cerebral arteries, consistent with ischemic stroke. Pulmonary and splenic infarcts were also found after CT of the chest. The age of the patient and the absence of serious concomitant cardiovascular diseases place the emphasis on the capacity of SARS-CoV-2 infection to be an independent cerebrovascular risk factor. Increased levels of D-dimer and positivity to ß2-glycoprotein antibodies could confirm the theory of endothelial activation and hypercoagulability, but other mechanisms - still under discussion - should not be excluded.

BoNT-A for Post-Stroke Spasticity: Guidance on Unmet Clinical Needs from a Delphi Panel Approach.

There is extensive literature supporting the efficacy of botulinum toxin (BoNT-A) for the treatment of post-stroke spasticity, however, there remain gaps in the routine management of patients with post-stroke spasticity. A panel of 21 Italian experts was selected to participate in this web-based survey Delphi process to provide guidance that can support clinicians in the decision-making process. There was a broad consensus among physicians that BoNT-A intervention should be administered as soon as the spasticity interferes with the patients' clinical condition. Patients monitoring is needed over time, a follow-up of 4-6 weeks is considered necessary. Furthermore, physicians agreed that treatment should be offered irrespective of the duration of the spasticity. The Delphi consensus also stressed the importance of patient-centered goals in order to satisfy the clinical needs of the patient regardless of time of onset or duration of spasticity. The findings arising from this Delphi process provide insights into the unmet needs in managing post-stroke spasticity from the clinician's perspective and provides guidance for physicians for the utilization of BoNT-A for the treatment of post-stroke spasticity in daily practice.

Transcranial Direct Current Stimulation Combined with Botulinum Neurotoxin Type A Injections for Treatment of Upper Limb Intention Tremor in Multiple Sclerosis: A Case Report.

Upper limb intention tremor is a common cause of disability in multiple sclerosis (MS). Transcranial direct current stimulation (tDCS) is an emerging form of brain stimulation used to improve sensorimotor impairments in many neurological disorders. Here, we describe a combined therapeutic approach with botulinum neurotoxin type A (BoNT-A) and tDCS for the treatment of upper limb tremor in a patient with MS. We administered a cathodal tDCS 15 days after the injections of BoNT-A. Both post-injection and post-stimulation evaluation revealed a considerable improvement of the tremor. This approach positively affected the patient's activities of daily living. Our case report shows a safe and beneficial effect of tDCS in the treatment of action tremor in MS especially as a possible adjunctive synergic treatment with BoNT-A injections.

Effectiveness of robotic balance training on postural instability in patients with mild Parkinson's disease: A pilot, single blind, randomized controlled trial.

OBJECTIVE: To examine whether tailored robotic platform training could improve postural stability compared with conventional balance treatment in patients with mild Parkinson's disease.  Design: Randomized single-blind pilot study. SUBJECTS: Twenty-two patients with mild Parkinson's disease (Hoehn and Yahr scale; HandY 1-2). METHODS: Patients were randomly assigned to an experimental group for robotic balance training and to a control group for conventional balance training. Each patient received 20 treatments (45 min/session, 5 times/week). Blinded evaluations were conducted before and after the treatment and 1 month post-treatment. Primary outcome measures were Mini BESTest, and Berg Balance Scale; secondary outcome measures were 10-Meter Walk Test, Five Times Sit to Stand Test, and Parkinson's Disease Questionnaire 39. RESULTS: Primary outcome measures in patients in both the experimental and control groups improved significantly after the balance treatment. Similar results were found for all the secondary outcome measures. The experimental group performed significantly better than the control group at both post-intervention and follow-up evaluation in the primary outcomes (p < 0.05). No significant differences be-tween groups were found in secondary outcomes. CONCLUSION: Robot-assisted balance training may be a promising tool to improve postural stability in patients with mild Parkinson's disease.

Localized muscle vibration in the treatment of motor impairment and spasticity in post-stroke patients: a systematic review.

INTRODUCTION: During the last decades, many studies have been carried out to understand the possible positive effects of vibration therapy in post-stroke rehabilitation. In particular, the use of localized muscle vibration (LMV) seems to have promising results. The aim of this systematic review was to describe the use of LMV in post-stroke patients to improve motor recovery, reducing spasticity and disability in both upper and lower limb. EVIDENCE ACQUISITION: A search was conducted on PubMed, Scopus, Pedro and REHABDATA electronic database. Only randomized controlled trials have been included, excluding no-localized vibratory treatments and other pathological conditions. Fourteen studies met the inclusion criteria and were included in this review. EVIDENCE SYNTHESIS: Collectively, the studies involved 425 stroke patients. Most studies included chronic stroke patients (ten) and treated only the upper limb (eleven). There is evidence that LMV therapy is effective in reducing spasticity and improving motor recovery, especially when associated with conventional physical therapy. CONCLUSIONS: LMV may be a feasible and safe tool to be integrated into traditional and conventional neurorehabilitation programs for post-stroke patients to reduce spasticity. Analysis of the available clinical trials do not allow us to indicate vibration therapy as effective in functional motor recovery, despite some studies showed encouraging results. Further studies, with larger size of homogeneous patients and with a shared methodology are needed to produce more reliable data, especially on the lower limb.

Discontinuation of botulinum neurotoxin type-A treatment during COVID-19 pandemic: an Italian survey in post stroke and traumatic brain injury patients living with spasticity.

BACKGROUND: The COVID-19 pandemic has affected health-care systems worldwide, including the outpatient spasticity care with botulinum neurotoxin toxin type A (BoNT-A). AIM: The aim of this study was to investigate the impact of discontinuation of BoNT-A treatment on patients living with spasticity during the COVID-19 quarantine. DESIGN: A multicentric cross-sectional study. SETTING: Outpatients setting. POPULATION: Patients with spasticity after stroke and traumatic brain injury treated with BoNT-A. METHODS: A phone-based survey was conducted from March to May, 2020. Based on the International Classification of Functioning, Disability and Health (ICF), an ad hoc questionnaire CORTOX (CORonavirus TOXin survey) was developed to investigate patients' experiences following the discontinuation of their usual treatment for spasticity due to the lockdown and its implication on their health perception. It assessed patients' condition and explored different ICF domains related to spasticity: unpleasant sensations, mobility, self-care, facilitators and psychosocial factors. The sum of those represented the CORTOX score (Max 142). The questionnaire also collected data about the impact of COVID-19 on patients' wellbeing (mood, sleep, relationships, community life, motivation). RESULTS: A total of 151 participants completed the survey. Most participants (72.2%) experienced a worsening in perceived spasticity, 53% got worse in independence and 70.9% had a negative impact on quality of life. The mean CORTOX score was 52.85±27.25, reflecting a perceived worsening in all ICF domains investigated. Moderate to strong correlations were found between different sub-scores of the questionnaire and severity of spasticity (P<0.001). COVID-19 psychosocial related factors were associated with loss of independence (P<0.05) but only mood was associated with worsening of spasticity (P<0.001). The lack of rehabilitation therapy was significantly associated with the worsening of independence but not with the worsening of spasticity. Finally, respondents reported that BoNT-A was useful to their condition and should not be discontinued. CONCLUSIONS: The discontinuation of BoNT-A treatment was associated with worsening of activities and participation and perceived spasticity. COVID-19 related problems and rehabilitation showed an association with loss of independence. CLINICAL REHABILITATION IMPACT: This study will provide useful information in the field of spasticity management using a patient's centred approach, with consistent quantitative and qualitative information.

Combined Effects of Isokinetic Training and Botulinum Toxin Type A on Spastic Equinus Foot in Patients with Chronic Stroke: A Pilot, Single-blind, Randomized Controlled Trial.

Botulinum toxin A (BoNT-A) has been shown effective for poststroke lower limb spasticity. Following injections, a wide range of multidisciplinary approach has been previously provided. The purpose of this pilot, single-blind, randomized controlled trial was to determine whether BoNT-A combined with a regime of a four-week ankle isokinetic treatment has a positive effect on function and spasticity, compared with BoNT-A alone. Secondly, the validity of the use of an isokinetic dynamometer to measure the stretch reflex at the ankle joint and residual strength has been investigated. Twenty-five chronic stroke patients were randomized to receive combined treatment (n = 12; experimental group) or BoNT-A alone (n = 13; control group). Outcome measures were based on the International Classification of Functioning, Disability and Health. An isokinetic dynamometer was also used for stretch reflex and strength assessment. Patients were evaluated at baseline (t0), after five (t1) and eight weeks after the injection (t2). The experimental group reported significantly greater improvements on lower limb spasticity, especially after eight weeks from baseline. Gait speed (10-m walk test) and walking capacity (6-min walking test) revealed statistically significantly better improvement in the experimental than in control group. Peak resistive ankle torque during growing angular velocities showed a significant reduction at the higher velocities after BoNT-A injections in the experimental group. Peak dorsiflexor torque was significantly increased in the experimental group and peak plantarflexor torque was significantly decreased in control group. Alternative rehabilitation strategies that combine BoNT-A and an intense ankle isokinetic treatment are effective in reducing tone and improving residual strength and motor function in patients with chronic hemiparesis.

Botulinum Toxin Type A for the Treatment of Lower Limb Spasticity after Stroke.

Post-stroke lower limb spasticity impairs balance and gait leading to reduced walking speed, often increasing wheelchair use and caregiver burden. Several studies have shown that appropriate treatments for lower limb spasticity after stroke include injections of botulinum toxin type A (BoNT-A), phenol or alcohol, surgical correction and a rehabilitation program. In the present article, we review the safety and effectiveness of BoNT-A for the treatment of lower limb spasticity after stroke, with a focus on higher doses of BoNT-A. The cumulative body of evidence coming from the randomized clinical trials and open-label studies selected in the article suggest BoNT-A to be safe and efficacious in reducing lower limb spasticity after stroke. Studies of high doses of BoNT-A also showed a greater reduction of severe post-stroke spasticity. In stroke survivors with spasticity of the ankle plantar-flexor muscles, a combined approach between surgery and BoNT-A can be indicated. However, controversy remains about improvement in motor function relative to post-stroke spasticity reduction after BoNT-A treatment.

Adjuvant treatments associated with botulinum toxin injection for managing spasticity: An overview of the literature.

BACKGROUND AND OBJECTIVE: A wide range of adjunct therapies after botulinum toxin administration have been proposed. The aim of the present paper is to provide an overview of major writings dealing with adjuvant (non-pharmacological) treatments associated with botulinum toxin for managing spasticity in order to provide some up-to-date information about the usefulness of the most commonly used procedures. METHODS: The literature in PubMed was searched with the MeSH terms botulinum toxins, muscle spasticity, physical therapy modalities, and rehabilitation. The results were limited to studies focusing on adjuvant treatments associated with botulinum toxin for managing spasticity. We excluded papers on the use of non-drug treatments for spasticity not associated with botulinum toxin serotype A (BoNT-A) injection. Relevant literature known to the authors along with this complementary search represented the basis for this overview of the literature. RESULTS: Adhesive taping and casting effectively improved the botulinum toxin effect in patients with upper- and lower-limb spasticity. There is level 1 evidence that casting is better than taping for outcomes including spasticity, range of motion and gait. However, consensus about their most appropriate timing, duration, target and material is lacking. In terms of physical modalities combined with botulinum toxin injection, we found level 1 evidence that extracorporeal shock wave therapy is better than electrical stimulation for some post-injection outcomes including spasticity and pain. Furthermore, electrical stimulation of injected muscles might be useful to boost the toxin effect. However, the best stimulation protocol has not been defined. In addition, we found level 2b evidence that whole-body vibration therapy might reduce spasticity with cerebral palsy. CONCLUSION: Future research in this field should focus on investigating the most appropriate post-injection treatment protocol for each goal to achieve.

Intra-articular injection of botulinum toxin type A for shoulder pain in glenohumeral osteoarthritis: a case series summary and review of the literature.

INTRODUCTION: Shoulder pain is one of the most common musculoskeletal diseases, and can be due to glenohumeral osteoarthritis, rotator cuff tear, impingement, tendinitis, adhesive capsulitis, and subacromial bursitis. Several therapies have been proposed, including steroids, nonsteroidal anti-inflammatory drugs, intra-articular injections, and physical therapies. Many published studies have reported on the employment of botulinum toxin type A (BoNT-A) to reduce pain in subjects with neurological and musculoskeletal diseases by inhibiting substance P release and other inflammatory factors. METHODS: In the present article, we briefly update current knowledge regarding intra-articular BoNT therapy, reviewing existing literature on intra-articular use of BoNT-A, including nonrandomized and randomized prospective and retrospective cohort studies and case series published from December 1989 to November 2017. We also describe a case series of six subjects treated with intra-articular injection of incobotulinumtoxin A for the treatment of pain deriving from osteoarthritis. CONCLUSION: Intra-articular BoNT-A is effective and minimally invasive. Pain reduction with an increase in shoulder articular range of motion in our experience confirms the effectiveness of BoNT-A injection for the management of this syndrome.

Ultrasonographic Evaluation of Botulinum Toxin Injection Site for the Medial Approach to Tibialis Posterior Muscle in Chronic Stroke Patients with Spastic Equinovarus Foot: An Observational Study.

The tibialis posterior muscle is a frequent target for injection of botulinum toxin during the management of spastic equinovarus foot in adults with post-stroke spasticity. Although it is deep-seated, the needle insertion into the tibialis posterior muscle is usually performed using anatomical landmarks and safety information obtained from healthy subjects and cadavers. Our aim was to evaluate the botulinum toxin injection site for the medial approach to the tibialis posterior muscle in chronic stroke patients with spastic equinovarus foot. Forty-six patients were evaluated at the affected middle lower leg medial surface with ultrasonography according to the following parameters: tibialis posterior muscle depth, thickness, and echo intensity. As to the spastic tibialis posterior, we found a mean muscle depth of 26.5 mm and a mean muscle thickness of 10.1 mm. Furthermore we observed a median tibialis posterior muscle echo intensity of 3.00 on the Heckmatt scale. The tibialis posterior muscle thickness was found to be inversely associated with its depth (p < 0.001) and echo intensity (p = 0.006). Furthermore, tibialis posterior muscle depth was found to be directly associated with its echo intensity (p = 0.004). Our findings may usefully inform manual needle placement into the tibialis posterior for the botulinum toxin treatment of spastic equinovarus foot in chronic stroke patients.

Change in Coefficient of Fatigability Following Rapid, Repetitive Movement Training in Post-Stroke Spastic Paresis: A Prospective Open-Label Observational Study.

BACKGROUND: In post-stroke patients, the possibility of performing an active ankle dorsiflexion movement is favorable for the recovery of gait. Moreover, the fatigue due to repetitive active ankle dorsiflexion could reduce the speed gait. We assessed the change in coefficient of fatigability of active ankle dorsiflexion after a home-based self-rehabilitative procedure in post-stroke patients. METHODS: In a prospective open-label observational study conducted in 2 university hospitals, a home-based self-rehabilitation treatment comprising two 12-minute sessions per day (3 times per week for 3 months) was performed by 10 outpatients with post-stroke lower limb impairment. Each session consisted of three 1-minute series of repeated active ankle dorsiflexion efforts at maximal speed on the paretic side, each one followed by 3-minute bouts of triceps surae stretch. Coefficients of fatigability of dorsiflexion and 10-meter barefoot ambulation speed were evaluated at baseline and at the end of the program. RESULTS: At 3 months of follow-up, there was a decrease in the coefficients of fatigability of ankle dorsiflexion, both with knee flexed and extended (respectively from 8% to 2% and from 6% to 2%; P < .01), associated with an increase in comfortable ambulation speed (from .24 to .26 m/s; P < .05). CONCLUSIONS: The reduction of coefficient of fatigability of ankle dorsiflexion, together with walking speed improvement, suggested the effectiveness of self-rehabilitation using alternated periods of self-stretch and rapid alternating efforts in the paretic lower limb after stroke.

Ultrasound-Guided Injection of Botulinum Toxin Type A for Piriformis Muscle Syndrome: A Case Report and Review of the Literature.

Piriformis muscle syndrome (PMS) is caused by prolonged or excessive contraction of the piriformis muscle associated with pain in the buttocks, hips, and lower limbs because of the close proximity to the sciatic nerve. Botulinum toxin type A (BoNT-A) reduces muscle hypertonia as well as muscle contracture and pain inhibiting substance P release and other inflammatory factors. BoNT-A injection technique is important considering the difficult access of the needle for deep location, the small size of the muscle, and the proximity to neurovascular structures. Ultrasound guidance is easy to use and painless and several studies describe its use during BoNT-A administration in PMS. In the present review article, we briefly updated current knowledge regarding the BoNT therapy of PMS, describing also a case report in which this syndrome was treated with an ultrasound-guided injection of incobotulinumtoxin A. Pain reduction with an increase of hip articular range of motion in this patient with PMS confirmed the effectiveness of BoNT-A injection for the management of this syndrome.

Postural and Balance Disorders in Patients with Parkinson's Disease: A Prospective Open-Label Feasibility Study with Two Months of Action Observation Treatment.

Action observation treatment has been proposed as therapeutic option in rehabilitation of patients affected by Parkinson's disease (PD) to improve freezing of gait episodes. The purpose of this prospective open-label feasibility study was to evaluate the impact of 8-week action observation training (video-therapy) for the treatment of postural instability and balance impairment in PD patients. Fifteen PD patients aged under 80 years with scores of 1 to 3 on the Hoehn and Yahr staging and without evidence of freezing of gait were recruited. They underwent 24 sessions of video-therapy training based on carefully watching video clips on motor tasks linked to balance, subsequently performing the same observed movements. No statistically significant differences were observed in the identified outcome measures with the Berg Balance Scale and the Activities-Specific Balance Confidence Scale after two months of follow-up. In the present study, a short course of action observation treatment seems to be not effective in reducing balance impairments and postural instability in patients affected by mild to moderate PD. Further studies with larger samples, longer follow-up period, and standardized protocols of action observation treatment are needed to investigate the effects of this rehabilitation technique in the management of postural and balance disorders of PD patients.