Triceps Surae Muscle Characteristics in Spastic Hemiparetic Stroke Survivors Treated with Botulinum Toxin Type A: Clinical Implications from Ultrasonographic Evaluation

Equinovarus foot is one of the most commonly spasticity related conditions in stroke survivors, leading to an impaired gait and poor functional performances. Notably, spastic muscles undergo a dynamic evolution following typical pathophysiological patterns. Botulinum Neurotoxin Type A (BoNT-A) is the gold standard for focal spasticity treatment, and ultrasound (US) imaging is widely recommended to guide injections and monitor muscle evolution. The role of BoNT-A in influencing muscle fibroadipose degeneration is still unclear. In this study, we analyzed medial gastrocnemius (MG) and soleus (SOL) US characteristics (cross-sectional area, muscle thickness, pennation angle, and mean echo intensity) in 53 patients. MG and SOL alterations, compared to the unaffected side, depend on the spasticity only and not on the BoNT-A treatment. In functionally preserved patients (functional ambulation classification, FAC > 3; modified Ashworth scale, MAS ≤ 2), the ultrasonographic changes of MG compared to ipsilateral SOL observed in the paretic limb alone seems to be due to histological, anatomical, pathophysiological, and biomechanical differences between the two muscles. In subjects with poor walking capability and more severe spasticity, such ipsilateral difference was found in both calves. In conclusion, BoNT-A does not seem to influence muscle degeneration. Similar muscles undergo different evolution depending on the grade of walking deficit and spasticity.

Review of available data for the efficacy and effectiveness of nabiximols oromucosal spray (Sativex) in multiple sclerosis patients with moderate to severe spasticity

Background: Sativex (USAN: nabiximols) oromucosal spray is indicated for treatment of multiple sclerosis (MS) patients with moderate to severe spasticity and inadequate response to other antispasticity medications who demonstrate clinically significant improvement during an initial trial of therapy. This narrative review investigated the efficacy and effectiveness of nabiximols oromucosal spray for moderate to severe MS spasticity by examining spasticity 010 Numerical Rating Scale (NRS) data from interventional and observational studies which featured a 4-week trial period as per the European Union approved label. Summary: Across both study types, clinically relevant and statistically significant reductions in mean MS spasticity 0–10 NRS scores were measured soon after treatment start and were maintained in the mid to long term in treatment responders. Initial responder rates (≥ 20% NRS improvement from baseline at week 4) ranged from 47.6% to 81.4%, tending lower in the randomized clinical trials setting. Clinically relevant responder rates (≥ 30% NRS improvement from baseline at week 12) were similar between study types (range 3041%) except for one outlier (74% in an observational study). Two open studies reported treatment continuation for ≥ 18 months in approximately half of patients who initiated treatment. In most longer-term studies, symptomatic improvement in MS spasticity was maintained at mean daily dosages of about 67 sprays/day. Safety was consistent with the known profile of nabiximols. Key messages: Experimental and observational studies of nabiximols oromucosal spray recorded similar findings. About half to two-thirds of MS patients who begin treatment will perceive initial symptomatic relief of spasticity within the 4-week trial period. About 40% of patients who initiate treatment will reach the ≥ 30% NRS improvement threshold at 3 months, comprising the majority of patients who continue long-term treatment. A trial of therapy with nabiximols is useful to identify patients most likely to gain longer-term improvement in spasticity symptoms and discontinue those with insufficient benefit.

Effects of 60 Min Electrostimulation With the EXOPULSE Mollii Suit on Objective Signs of Spasticity

Background: The EXOPULSE Mollii method is an innovative full-body suit approach for non-invasive electrical stimulation, primarily designed to reduce disabling spasticity and improve motor function through the mechanism of reciprocal inhibition. This study aimed to evaluate the effectiveness of one session of stimulation with the EXOPULSE Mollii suit at different stimulation frequencies on objective signs of spasticity and clinical measures, and the subjective perceptions of the intervention.Methods: Twenty patients in the chronic phase after stroke were enrolled in a cross-over, double-blind controlled study. Electrical stimulation delivered through EXOPULSE Mollii was applied for 60 min at two active frequencies (20 and 30 Hz) and in OFF-settings (placebo) in a randomized order, every second day. Spasticity was assessed with controlled-velocity passive muscle stretches using the NeuroFlexor hand and foot modules. Surface electromyography (EMG) for characterizing flexor carpi radialis, medial gastrocnemius, and soleus muscles activation, Modified Ashworth Scale and range of motion were used as complementary tests. Finally, a questionnaire was used to assess the participants' perceptions of using the EXOPULSE Mollii suit.Results: At group level, analyses showed no significant effect of stimulation at any frequency on NeuroFlexor neural component (NC) and EMG amplitude in the upper or lower extremities (p > 0.35). Nevertheless, the effect was highly variable at the individual level, with eight patients exhibiting reduced NC (>1 N) in the upper extremity after stimulation at 30 Hz, 5 at 20 Hz and 3 in OFF settings. All these patients presented severe spasticity at baseline, i.e., NC > 8 N. Modified Ashworth ratings of spasticity and range of motion did not change significantly after stimulation at any frequency. Finally, 75% of participants reported an overall feeling of well-being during stimulation, with 25% patients describing a muscle-relaxing effect on the affected hand and/or foot at both 20 and 30 Hz.Conclusions: The 60 min of electrical stimulation with EXOPULSE Mollii suit did not reduce spasticity consistently in the upper and lower extremities in the chronic phase after stroke. Findings suggest a need for further studies in patients with severe spasticity after stroke including repeated stimulation sessions.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT04076878, identifier: NCT04076878.

Intrathecal baclofen therapy for severe spasticity in an adult with tethered cord syndrome: a case report

Background Patients with tethered cord syndrome often suffer severe spasticity. To the best of our knowledge, intrathecal baclofen (ITB) therapy in a patient with tethered cord syndrome has not been reported previously. We describe a case in which ITB therapy was useful for treating severe spasticity in an adult with tethered cord syndrome. Case presentation We present the case of a 50-year-old Japanese woman with tethered cord syndrome and related conditions suffering from severe spasticity and pain in the lower limbs. She was born with a lumbosacral myelomeningocele, which was closed in the neonatal period. For 4–5 years before this presentation, spasticity in the lower limbs had been exacerbated without any obvious cause. She received rehabilitation and pharmacotherapy from a local doctor, but symptoms were unimproved, and her previous doctor referred her to this department. A test with 50 μg of intrathecally delivered baclofen showed total relief of spasticity and pain, so a pump was implanted for continuous baclofen delivery. During 24 months of follow-up, spasticity has remained under excellent control with baclofen at 38.5–41.0 μg/day. Conclusions ITB therapy proved extremely effective in this adult with severe spasticity from tethered code syndrome.

Baclofen bridging, weaning protocol and pain management of a person with T6 paraplegia who required removal of intrathecal baclofen pump due to wound infection

Intrathecal baclofen is recognised as an effective treatment option for severe symptoms of segmental spasticity after spinal cord injury. We present our experience of a case of a patient who was admitted to our centre for elective intrathecal baclofen pump revision surgery, but postsurgical complications of a blocked catheter and subsequent wound infections meant the pump had to be removed. In this case, treatment of severe spasticity and nociceptive pain was required while avoiding potentially lethal side effects of sudden baclofen withdrawal. We suggest an effective bridging and weaning protocol for oral drug titration to treat spasticity and pain as a blended syndrome in this challenging situation.

INTRATHECAL BACLOFEN PUMP FOR SPASTIC HYPERTONIA FOLLOWING PENETRATING BRAIN INJURY

Management of severe spasticity following penetrating brain injury is often a difcult problem. Orally administered medications generally offer limited benets. Intrathecally administered baclofen has been shown to be effective in patients with spasticity caused by spinal cord injury and stroke, however, the effectiveness of ITB for spasticity related to penetrating brain injury is not well established. We reported two cases of spastic hypertonia following gunshot injury to brain with brief review of literature upon role of intrathecal baclofen pump (ITB) in cortical spastic hypertonia

Flumazenil therapy for a gabapentin-induced coma: a case report

Background Spasticity and neuropathic pain are common in patients after spinal cord injury and negatively affect patients’ quality of life. Gabapentin and baclofen are frequently used to treat these conditions. We present a flumazenil-reversed gabapentin-induced coma case, which, to our knowledge, is the second one described in scientific literature. Case presentation A 70-year-old Caucasian man was admitted to our neurorehabilitation ward following a fall with cervical trauma that resulted in immediate tetraplegia. During his stay, he suffered from lower limb pain, both neuropathic and due to severe spasticity. Gradual baclofen and gabapentin administration was prescribed, with reduction in both pain and spasticity. One morning, the patient was found unresponsive, with a Glasgow Coma Score of 3. Head computerized tomography, electrocardiogram, electroencephalogram, vital signs, blood tests, breathing, and blood oxygenation were normal. Renal and liver failure were ruled out. Intravenous 0.25 mg of flumazenil (Anexate) was administered, resulting in complete neurocognitive recovery with a Glasgow Coma Score of 15. Discussion and conclusions This case report highlights the importance of the individual response to certain pharmacological agents and suggests that further studies need to be conducted both on flumazenil and gabapentin pharmacodynamics to better understand their molecular–receptor activity, and on possible multiple flumazenil mechanisms of action, beyond its classical strict benzodiazepine antagonist action.

Robotic rehabilitation for end-effector device and botulinum toxin in upper limb rehabilitation in chronic post-stroke patients: an integrated rehabilitative approach

Background Determine the effects of an integrated rehabilitation protocol, including botulinum toxin and conventional rehabilitation exercise plus end-effector (EE) robotic training for functional recovery of the upper limb (UL) compared to training with the robot alone in post-chronic stroke patients with mild to severe spasticity, compared to training with the robot alone. Methods In this prospective, observational case-control study, stroke patients were allocated into 2 groups: robot group (RG, patients who underwent robotic treatment with EE) and robot-toxin group (RTG, patients who in addition have carried out the injection of botulinum toxin for UL recovery). All patients were assessed by Fugl-Meyer Assessment (FMA), Motricity Index (MI), modified Ashworth scale (MAS), numeric rating scale (NRS), Box and Block Test (BBT), Frenchay Arm Test (FAT), and Barthel Index (BI) at baseline (T0), T1 (end of treatment), and T2 (3 months of follow-up). Results Forty-four patients were included and analyzed (21RG; 23RTG). From the analysis between groups, the results suggested how there was a statistically significant difference in favor of RTG, specifically ΔT0-T1 and ΔT0-T2 for B&B p = 0.009 and p = 0.035; ΔT0-T1 and ΔT0-T2 for FAT with p = 0.016 and p = 0.031; ΔT0-T1 for MAS shoulder p = 0.016; ΔT0-T1 and ΔT0-T2 with p = 0.010 and p = 0.005 for MAS elbow; and ΔT0-T1 and ΔT0-T2 with p = 0.001 and p = 0.013 for MAS wrist. Conclusion Our results suggest, in line with the literature, a good efficacy in the reduction of spasticity and in the improvement of the function of the UL, with the reduction of pain, adopting a rehabilitation protocol integrated with BoTN, robot-assisted training, and traditional physiotherapy.

Prevalence and Risk Factors for Spasticity After Stroke: A Systematic Review and Meta-Analysis

Background: Spasticity is a common sequela of stroke. The incidence of poststroke spasticity (PSS) has not been systematically reviewed in recent years, and some risk factors remain debated. This systematic review and meta-analysis was conducted to determine the prevalence and risk factors for PSS.Methods: We searched electronic databases (PubMed, Embase, Cochrane Library, CNKI, WANFANG and CBM) inception to May 12, 2020. Observational studies summarizing the incidence or risk factors for PSS were included. Only cohort studies were enrolled in meta-analysis. For risk factors examined in at least three different studies, we combined effects into odds ratios (OR) and 95% confidence intervals (CI).Results: One thousand four hundred sixty-seven studies were retrieved and 23 were involved in meta-analysis. The pooled prevalence of spasticity after stroke was 25.3% and that after the first-ever stroke was 26.7%. The incidence of spasticity after the first-ever stroke with paresis was 39.5%. The prevalence of disabling or severe spasticity (MAS ≥ 3) in stroke patients with paresis was 9.4% (95% CI 0.056–0.133), and severe spasticity was 10.3% (95% CI 0.058–0.149). Moderate to severe paresis (OR = 6.573, 95% CI 2.579–16.755, I2 = 0.0%), hemorrhagic stroke (OR = 1.879, 95% CI 1.418–2.490, I2 = 27.3%) and sensory disorder were risk factors for PSS.Conclusions: The incidence of PSS was significantly higher in stroke patients with paresis. Patients with moderate to severe paresis and sensory disorder should be closely followed up. The role of hemorrhagic stroke in predicting PSS remains to be further explored.