Botulinum Toxin-A High-Dosage Effect on Functional Outcome and Spasticity-Related Pain in Subjects with Stroke.

Stroke patients can develop spasticity and spasticity-related pain (SRP). These disorders are frequent and can contribute to functional limitations and disabling conditions. Many reports have suggested that higher doses than initially recommended of BTX-A can be used effectively and safely, especially in the case of severe spasticity; however, whether the treatment produces any benefit on the functional outcome and SRP is unclear. Studies published between January 1989 and December 2022 were retrieved from MEDLINE/PubMed, Embase, and Cochrane Central Register. Only obabotulinumtoxinA (obaBTX-A), onabotulinumtoxinA, (onaBTX-A), and incobotulinumtoxinA (incoBTX-A) were considered. The term "high dosage" indicates ≥600 U. Nine studies met the inclusion criteria. Globally, 460 subjects were treated with BTX-A high dose, and 301 suffered from stroke. Studies had variable method designs, sample sizes, and aims. Only five (55.5%) reported data about the functional outcome after BTX-A injection. Functional measures were also variable, and the improvement was observed predominantly in the disability assessment scale (DAS). SRP pain was quantified by visual analog scale (VAS) and only three studies reported the BTX-A effect. There is no scientific evidence that this therapeutic strategy unequivocally improves the functionality of the limbs. Although no clear-cut evidence emerges, certain patients with spasticity might obtain goal-oriented improvement from high-dose BTX-A. Likewise, data are insufficient to recommend high BTX dosage in SRP.

Case Report: Functional Outcome of COVID-19 Subjects With Myasthenia Gravis and Critical Illness Polyneuropathy.

Background: The COVID-19 disease can affect subjects suffering from myasthenia gravis (MG) and worsen its clinical course, leading to intensive care unit (ICU) admission. Critically ill subjects can develop a neuromuscular complication called ICU-acquired weakness (ICUAW). This disorder has also been detected in ICU subjects with COVID-19, but the association between MG and ICUAW has never been described in critically ill patients. We describe the case and functional outcome of a COVID-19 patient suffering from MG who developed critical illness polyneuropathy (CIP). Case Presentation: A 66-year-old man with a history of hypertension and ocular MG had COVID-19 and required ICU admission. The patient underwent mechanical ventilation and tracheotomy and was treated with remdesivir and corticosteroids. Fifteen days after admission, he complained of tetraparesis without the ocular involvement that remained unchanged despite the increase in anticholinesterase therapy. The length of stay (LOS) in ICU was 35 days. On day 2 of admission, the patient underwent a frontal muscle jitter study that confirmed the MG, and electroneurography (ENG) and electromyography (EMG) that showed overlapping ICUAW with electrophysiological signs characteristic of CIP. The cerebrospinal fluid (CSF) showed normal pressure, cell count, and protein levels (<45 mg/dl) without albumin-cytologic disassociation. The CSF/serum glucose ratio was normal. The CSF culture for possible organisms, laboratory tests for autoimmune disorders, the panel of antiganglioside antibodies, and the paraneoplastic syndrome were negative. Strength and functional outcomes were tested with the MRC scale, the DRS, Barthel scale, and the Functional Independence Measure (FIM) at admission, discharge, and follow-up. Muscular strength improved progressively, and the MRC scale sum-score was 50 at discharge. Anticholinesterase therapy with pyridostigmine at a dosage of 30 mg 3 times daily, which the patient was taking before COVID-19, was resumed. His motor abilities recovered, and functional evaluations showed full recovery at follow-up. Conclusion: In the described subject, the coexistence of both neuromuscular disorders did not affect the clinical course and recovery, but the question remains about generalization to all patients with MG. The rehabilitation interventions might have facilitated the outcome.

Recovery and long term functional outcome in people with critical illness polyneuropathy and myopathy: a scoping review.

BACKGROUND: Intensive care unit acquired weakness (ICUAW), embraces an array of disorders labeled "critical illness polyneuropathy" (CIP), "critical illness myopathy" (CIM) or "critical illness polyneuromyopathy" (CIPNM). Several studies have addressed the various characteristics of ICUAW, but the recovery is still unclear. OBJECTIVE: The present review investigated the recovery and the long-term functional outcome of subjects with ICUAW, whether the types of ICUAW have different outcomes and whether there is any supporting evidence. METHODS: Literature search was performed from MEDLINE/PubMed, CINAHL, EMBASE, PeDro, Web of Science and Scopus. Inclusion criteria were: i) sample size including five or more subjects; ii) subjects who suffered from ICUAW and/or CIP, CIM and CIP/CIM; iii) ICUAW ascertained by EMG. Follow-ups longer than one year were defined as long-term. RESULTS: Twenty-nine studies met the inclusion criteria. In total, 788 subjects with ICUAW were enrolled: 159 (20.1%) died and 588 (74.6%) were followed. Of all the included patients, 613 (77.7%) had CIP, 82 (10.4%) CIM and 56 (7.1%) CIP/CIM. Overall, 70.3% of the subjects with ICUAW fully recovered. Seven (24.1%) studies had a follow-up longer than 1 year (range 2-8) with 173 (21.9%) subjects enrolled globally and 108 followed. Of these subjects, 88.8% gained full recovery. Most of the studies did not use proper functional scales and only 4 and 3 studies employed the Barthel scale and the Functional Independence Measure (FIM) scale. Differentiation between the types of ICUAW was performed in 7 studies, but only 3 studies reported that subjects with CIM had a better prognosis and earlier recovery than subjects with CIP/CIM. CONCLUSIONS: Subjects with ICUAW could achieve good recovery and could improve at follow-up. However, the quality of the published studies due to short follow-ups and the paucity of defined outcome measures require confirms.

Effectiveness of Robot-Assisted Upper Limb Training on Spasticity, Function and Muscle Activity in Chronic Stroke Patients Treated With Botulinum Toxin: A Randomized Single-Blinded Controlled Trial.

Background: The combined use of Robot-assisted UL training and Botulinum toxin (BoNT) appear to be a promising therapeutic synergism to improve UL function in chronic stroke patients. Objective: To evaluate the effects of Robot-assisted UL training on UL spasticity, function, muscle strength and the electromyographic UL muscles activity in chronic stroke patients treated with Botulinum toxin. Methods: This single-blind, randomized, controlled trial involved 32 chronic stroke outpatients with UL spastic hemiparesis. The experimental group (n = 16) received robot-assisted UL training and BoNT treatment. The control group (n = 16) received conventional treatment combined with BoNT treatment. Training protocols lasted for 5 weeks (45 min/session, two sessions/week). Before and after rehabilitation, a blinded rater evaluated patients. The primary outcome was the Modified Ashworth Scale (MAS). Secondary outcomes were the Fugl-Meyer Assessment Scale (FMA) and the Medical Research Council Scale (MRC). The electromyographic activity of 5 UL muscles during the "hand-to-mouth" task was explored only in the experimental group and 14 healthy age-matched controls using a surface Electromyography (EMGs). Results: No significant between-group differences on the MAS and FMA were measured. The experimental group reported significantly greater improvements on UL muscle strength (p = 0.004; Cohen's d = 0.49), shoulder abduction (p = 0.039; Cohen's d = 0.42), external rotation (p = 0.019; Cohen's d = 0.72), and elbow flexion (p = 0.043; Cohen's d = 1.15) than the control group. Preliminary observation of muscular activity showed a different enhancement of the biceps brachii activation after the robot-assisted training. Conclusions: Robot-assisted training is as effective as conventional training on muscle tone reduction when combined with Botulinum toxin in chronic stroke patients with UL spasticity. However, only the robot-assisted UL training contributed to improving muscle strength. The single-group analysis and the qualitative inspection of sEMG data performed in the experimental group showed improvement in the agonist muscles activity during the hand-to-mouth task. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03590314.

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.