Muscle Selection and Dosing in a Phase 3, Pivotal Study of AbobotulinumtoxinA Injection in Upper Limb Muscles in Children With Cerebral Palsy

Background: Guidelines recommend botulinum toxin-A in pediatric upper limb spasticity as part of routine practice. Appropriate dosing is a prerequisite for treatment success and it is important that injectors have an understanding on how to tailor dosing within a safe and effective range. We report upper limb dosing data from a phase 3 study of abobotulinumtoxinA injections in children with cerebral palsy.Methods: This was a double-blind, repeat-treatment study (NCT02106351). In Cycle 1, children were randomized to abobotulinumtoxinA at 2 U/kg control dose or clinically relevant 8 U/kg or 16 U/kg doses. Doses were divided between the primary target muscle group (PTMG, wrist or elbow flexors) and additional muscles tailored to clinical presentation. During Cycles 2–4, children received doses of 8 U/kg or 16 U/kg and investigators could change the PTMG and other muscles to be injected. Injection of muscles in the other upper limb and lower limbs was also permitted in cycles 2–4, with the total body dose not to exceed 30 U/kg or 1,000 U (whichever was lower) in the case of upper and lower limb treatment.Results: 212 children were randomized, of which 210 received ≥1 abobotulinumtoxinA injection. Per protocol, the elbow and wrist flexors were the most commonly injected upper limb muscles. Across all 4 cycles, the brachialis was injected in 89.5% of children (dose range 0.8–6 U/kg), the brachioradialis in 83.8% (0.4–3 U/kg), the flexor carpi ulnaris in 82.4% (0.5–3 U/kg) and the flexor carpi radialis in 79.5% (0.5–4 U/kg). Other frequently injected upper limb muscles were the pronator teres(70.0%, 0.3–3 U/kg). adductor pollicis (54.3%, 0.3-1 U/kg), pronator quadratus (44.8%, 0.1–2 U/kg), flexor digitorum superficialis (39.0%, 0.5-4 U/kg), flexor digitorum profundus (28.6%, 0.5–2 U), flexor pollicis brevis/opponens pollicis (27.6%, 0.3-1 U/kg) and biceps (27.1%, 0.5–6 U/kg). AbobotulinumtoxinA was well-tolerated at these doses; muscular weakness was reported in 4.3% of children in the 8 U/kg group and 5.7% in the 16 U/kg group.Conclusions: These data provide information on the pattern of injected muscles and dose ranges used in this study, which were well-tolerated. Per protocol, most children received injections into the elbow and wrist flexors. However, there was a wide variety of other upper limb muscles injected as physicians tailored injection patterns to clinical need.

Tuberculosis tenosynovitis of the wrist: a rare case report

Tuberculosis (TB) is a common disease of the Asian continent and has a varied presentation. Involvement of the musculoskeletal system is uncommon and presents in 10% of extrapulmonary tuberculosis. The atypical sites of tuberculous infection are the spine (51%) pelvis (12%), hip and femur (10%), knee and tibia (10%), and ribs (7%), but involvement of the wrist is rare. Tuberculosis tenosynovitis is a rare site of extra-articular TB. Delayed diagnosis and hence treatment is because it mimics many other disease processes and as a result, complications are common. Median nerve compression leading to carpal tunnel syndrome may also occur in these patients. Here, we present a case of tuberculous tenosynovitis involving the wrist flexors and the radial and ulnar bursae treated with surgery.

Relation Between Sensorimotor Rhythm During Motor Attempt/Imagery and Upper-Limb Motor Impairment in Stroke

Motor attempt (MA)/motor imagery (MI)-based brain–computer interface (BCI) is a newly developing rehabilitation technology for motor impairment. This study aims to explore the relationship between electroencephalography sensorimotor rhythm and motor impairment to provide reference for a BCI design. Twenty-eight stroke survivors with varying levels of motor dysfunction and spasticity status in the subacute or chronic stage were enrolled in the study to perform MA and MI tasks. Event-related desynchronization (ERD)/event-related synchronization (ERS) during and immediately after motor tasks were calculated. The Fugl–Meyer assessment scale (FMA) and the modified Ashworth scale (MAS) were applied to characterize upper-limb motor dysfunction and spasticity. There was a positive correlation between FMA total scores and ERS in the contralesional hemisphere in the MI task ( P < .05) and negative correlations between FMA total scores and ERD in both hemispheres in the MA task ( P < .05). Negative correlations were found between MAS scores of wrist flexors and ERD in the ipsilesional hemisphere ( P < .05) in the MA task. It suggests that motor dysfunction may be more correlated to ERS in the MI task and to ERD in the MA task while spasticity may be more correlated to ERD in the MA task.

Forearm muscle mitochondrial capacity and resting oxygen uptake: Relationship to symptomatic fatigue in persons with multiple sclerosis

Background Mitochondrial dysfunction has been implicated in the pathogenesis of multiple sclerosis (MS). Whether mitochondrial alterations are a function of ambulatory dysfunction or are of a non-ambulatory systemic nature is unclear. Objective To compare oxidative capacity, and rest muscle oxygen consumption (mVO2) in the upper limb of persons with multiple sclerosis (PwMS) to a control group (CON), whereby an upper limb would be comparatively independent of ambulation or deconditioning. Methods Near infra-red spectroscopy was used to measure oxidative capacity of the wrist flexors in PwMS (n = 16) and CON (n = 13). Oxidative capacity was indicated by the time constant (TC) of mVO2 recovery following brief wrist flexion contractions. Measurements included well-being, depression, symptomatic fatigue, disability, handgrip strength, cognition, and functional endurance. Analysis was by T-tests and Pearson correlations with p ≤ 0.05. Data are mean (SD). Results TC of mVO2 recovery was slower in PwMS (MS = 47(14) sec, CON = 36(11) sec; p = 0.03). No significant correlations were found between oxidative capacity and any other measures. Rest mVO2 was not different between groups, but correlated with symptomatic fatigue (r = 0.694, p = 0.003) and strength (0.585, p = 0.017) in PwMS. Conclusion Oxidative capacity was lower in the wrist flexors of PwMS, possibly indicating a systemic component of the disease. Within PwMS, rest mVO2 was associated with symptomatic fatigue.

Effect of Object Texture and Weight on Ipsilateral Corticospinal Influences During Bimanual Holding in Humans

We tested the hypothesis that the ipsilateral corticospinal system, like the contralateral corticospinal system, controls the threshold muscle length at which wrist muscles and the stretch reflex begin to act during holding tasks. Transcranial magnetic stimulation was applied over the right primary motor cortex in 21 healthy subjects holding a smooth or coarse block between the hands. Regardless of the lifting force, motor evoked potentials in right wrist flexors were larger for the smooth block. This result was explained based on experimental evidence that motor actions are controlled by shifting spatial stretch reflex thresholds. Thus, the ipsilateral corticospinal system is involved in threshold position control by modulating facilitatory influences of hand skin afferents on motoneurons of wrist muscles during bimanual object manipulation.

Clinical case of combined genetic pathology in a patient

Family hypercholesterolemia (HSX) is a form of genetically deterministic increase in blood lipid levels associated with a high risk of cardiovascular disease, usually at a young age. HSX is a common genetic disease found in the general population in most countries in 1:500 people. Clinically xantomas are found in achilles tendor and wrist flexors, lipoid arc of the cornea, concentration of total cholesterol and low-density lipoproteins is 4.911.6 mmol/l. Gilberts syndrome is a hereditary benign hyperbilirubinium, associated with a decrease in the functional activity of the liver enzyme uridinfosfat-glucuronosil transferase. Clinically, this syndrome appers in intermittent jaundice, which is provoked by physical activity, consumption of alcoholic beverages, insulation and an increase in the level of indirect bilirubin within 20100 micromol/ml. The article presents a rare clinical case of genetic combination of HSC SSC and Gilbert syndrome a young patient has and discusses the elevated bilirubin levels protective role in the atherosclerosis progression in Gilbert syndrome.

Effects of active isolated stretching on exercise-induced muscle damage in untrained subjects: a randomized controlled trial

Objective: To investigate the prophylactic effect of the active isolated stretching technique on exercise-induced muscle damage of wrist flexors. Method: The mixed model randomised controlled interventional study was conducted at the University of Sargodha, Sargodha, Pakistan, from November 2018 to May 2019, and comprised young adults who were untrained, sedentary and healthy who were randomly divided into intervention group A and control group B. Group A participants received self-assisted active isolated stretching before inducing muscle soreness of wrist flexors by eccentric exercises. Group B did not receive any intervention. The outcome measures were pain intensity, muscle soreness, pressure pain threshold, range of motion, and grip strength. Data were collected at baseline, after one hour, and daily from day 1 to 7 after inducing muscle soreness. Data were analysed using SPSS 21. Results: Of the 60 subjects, there were 30(50%) in each of the two groups. There were 14(23.3%) males and 46(76.7%) females. The overall mean age was 21.47±1.9 years. Group A showed early recovery in pain and muscle soreness compared to group B (p<0.05). Also, a limited deficit in the range of motion, grip strength, and pain pressure threshold was found in group A compared to group B (p<0.05). Conclusion: Active isolated stretching before strenuous, unaccustomed exercise was found to be useful in ameliorating the symptoms of muscle soreness. Key Words: Active isolated stretching, Muscle soreness, Exercise-induced muscle damage, Eccentric exercises. Continuous...

Meningoencephalitis case with listeriosis etiology in an immunocompetent female patient

Nervous forms of listeriosis are observed in 5%10% of persons suffering from this disease and in 75% of children with bacteriologically confirmed listeriosis as well. The most widespread clinical variant is Listeria meningitis, making up 15% of all cases of bacterial and serous meningitides. The mortality rate at neurolisteriosis reaches 30%40%. A case of acute meningoencephalitis associated with Listeria monocytogenes 4b in a 37-year-old immunocompetent woman is described. The disease was characterized by subacute onset, manifested intoxication, long-lasting and high-grade fever, cerebral coma, bulbar syndrome, right-side hemiparesis, bilateral hypertonus of the wrist flexors, strabism, anisocoria, manifested leukocytosis with leukocyte formula stab shift, ESR 4559 mm/hour. Cerebrospinal fluid test: cytosis 663 сells in 1 mcl, neutrophils 79%, lymphocytes 21%, protein 1451 mg/l, glucose 3.8 mmol/l. Diagnosis had been confirmed with detection of IgM against Listeria monocytogenes 4b in liquor using the indirect immunofluorescence reaction and Listeria monocytogenes by means of PCR. Antibacterial therapy had been conducted using Meropenem, Ampicillinum, endolumbal administration of 4 mg once daily of Gentamycinum combined with intravenous administration of 24 million of units/day of Penicillin. On day 50, she was transferred for rehabilitation treatment to the Department of Neurology.

Proprioceptive afferents differentially contribute to effortful perception of object heaviness and mass distribution

When humans handle a tool, such as a tennis racket or hammer, for the first time, they often wield it to determine its inertial properties, however, the mechanisms that contribute to perception of inertial properties are not fully understood. The goal of the present study was to investigate how proprioceptive afferents contribute to effortful perception of heaviness and mass distribution of a manually wielded object in the absence of vision. Blindfolded participants manually wielded a set of specially-designed experimental objects of different mass and mass distribution about the wrist at different wrist angles and wrist angular kinematics. By independently manipulating these variables, we aimed to elicit different levels of tonic and rhythmic activity in the muscle spindles of the wrist flexors and extensors and relate them to reported perceptual judgments of heaviness and length. Perception of heaviness and length were predominantly dependent on an object’s static moment and the moment of inertia, respectively. Manipulations of wrist angle and wrist angular kinematics affected perceptual judgments of heaviness and length in relatively opposite ways. As for wrist angle, ulnar deviation consistently resulted in an object being perceived heavier but shorter. Compared to static holding, wielding the object resulted in it being perceived heavier but wielding did not affect perceived length. These results suggest that proprioceptive afferents differentially contribute to effortful perception of object heaviness and mass distribution.