Myung Eun Chung

Botulinum Toxin for Neuropathic Pain: A Review of the Literature

Botulinum neurotoxin (BoNT), derived from Clostridium botulinum, has been used therapeutically for focal dystonia, spasticity, and chronic migraine. Its spectrum as a potential treatment for neuropathic pain has grown. Recent opinions on the mechanism behind the antinociceptive effects of BoNT suggest that it inhibits the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. There is some evidence showing the axonal transport of BoNT, but it remains controversial. The aim of this review is to summarize the experimental and clinical evidence of the antinociceptive effects, mechanisms, and therapeutic applications of BoNT for neuropathic pain conditions, including postherpetic neuralgia, complex regional pain syndrome, and trigeminal neuralgia. The PubMed and OvidSP databases were searched from 1966 to May 2015. We assessed levels of evidence according to the American Academy of Neurology guidelines. Recent studies have suggested that BoNT injection is an effective treatment for postherpetic neuralgia and is likely efficient for trigeminal neuralgia and post-traumatic neuralgia. BoNT could also be effective as a treatment for diabetic neuropathy. It has not been proven to be an effective treatment for occipital neuralgia or complex regional pain syndrome.

Characteristics of dysphagia in children with cerebral palsy, related to gross motor function.

ObjectiveThe aim of this study was to report the characteristics of dysphagia in children with cerebral palsy (CP), related to gross motor function. DesignVideofluoroscopic swallow study was performed in 29 children with CP, according to the manual of Logemann. Five questions about oromotor dysfunction were answered. Gross motor function level was classified by the Gross Motor Function Classification System Expanded and Revised. ResultsThe results of the videofluoroscopic swallowing studies showed that reduced lip closure, inadequate bolus formation, residue in the oral cavity, delayed triggering of pharyngeal swallow, reduced larynx elevation, coating on the pharyngeal wall, delayed pharyngeal transit time, multiple swallow, and aspiration were significantly more common in the severe group (Gross Motor Function Classification System Expanded and Revised IV or V). As for aspiration, 50% of the children with severe CP had problems, but only 14.3% of them with moderate (Gross Motor Function Classification System Expanded and Revised III) CP and none of them with mild CP had abnormalities. In addition, five of the seven aspiration cases occurred silently. ConclusionsThis study shows that dysphagia is closely related to gross motor function in children with CP. Silent aspiration was observed in the moderate to severe CP groups. Aspiration is an important cause of medical problems such as acute and chronic lung disease, and associated respiratory complications contribute significantly in increasing morbidity and mortality in these patient groups. Therefore, the authors suggest that early dysphagia evaluation including videofluoroscopic swallow study is necessary in managing feeding problems and may prevent chronic aspiration, malnutrition, and infections.

Botulinum toxin type A for neuropathic pain in patients with spinal cord injury.

To evaluate the analgesic effect of botulinum toxin type A (BTX‐A) on patients with spinal cord injury‐associated neuropathic pain.

Ischemic Stroke in Rats Enhances Bone Resorption in Vitro

We hypothesized that the formation and differentialtion of osteoclasts are accelerated and the potential of bone resorption is increased in the hemiplegic bone marrow in the early stage of stroke. We randomly divided white female Sprague-Dawley (SD) rats (n = 30) into two groups, stroke (n = 15) and sham group (n = 15). On the 7th day after stroke, after cutting away the epiphyses of the femurs and tibias, diaphyseal channels were flushed using α-minimum essential medium (α-MEM) and bone marrow cells were collected. Bone marrow stem cells, which were extracted from the femur and tibia, were cultured on the 7th day after middle cerebral artery occlusion. We then estimated the ratio of non-adherent cells to total bone marrow cells that included osteoclast precursor cells. After culturing these cells separately, cells that tested positive on the tartrate resistant acid phosphatase (TRAP) were counted and bone resorption was evaluated by using the OAAS™ plate. In comparison to the control group, the stroke group showed a higher increase of non-adherent cells in the hemiplegic side bone marrow. In addition, after the primary culture, the stroke group showed an increased number of TRAP positive cells and a higher degree of bone resorption estimated by OAAS™ plate. As a result, osteoclastogenesis and osteoclast differentiation are accelerated and the potential of bone resorption is increased in the hemiplegic bone marrow and these changes are detected as early as within the first week after middle cerebral artery occlusion in SD rats.

Comparative Study of Biological Activity of Four Botulinum Toxin Type A Preparations in Mice

BACKGROUND Units of available botulinum toxin preparations are not interchangeable, and the dose‐conversion ratios between such preparations remain controversial. OBJECTIVE To compare the efficacy and safety of four botulinum toxin type A preparations. MATERIALS AND METHODS Murine gastrocnemius compound muscle action potentials (CMAPs) were recorded before and after injecting the four botulinum toxin preparations (onabotulinumtoxinA, abobotulinumtoxinA, new botulinum toxin, and incobotulinumtoxinA). RESULTS In all preparations, CMAP amplitudes decreased until 4 days after receiving the injection and then gradually recovered. On postinjection day 84, the amplitudes returned to baseline in all groups except the high‐dose groups. CMAP amplitude in the contralateral limb also decreased up to postinjection days 4 to 7 and then gradually returned to baseline by postinjection day 28. CONCLUSION The dose‐conversion ratio between onabotulinumtoxinA and abobotulinumtoxinA was determined to be 1:2.6; previous reports of 1:3 were considered too high. A dose‐conversion ratio between onabotulinumtoxinA and new botulinum toxin of 1:1 was deemed appropriate. OnabotulinumtoxinA and incobotulinumtoxinA demonstrated a dose‐conversion ratio of 1:1.07. The efficacy of incobotulinumtoxinA was slightly lower than that of onabotulinumtoxinA. These dose‐conversion ratios are applicable solely from an efficacy standpoint and not for safety. This study was conducted in mice, so it may not translate perfectly to human applications.

Efficacy and Safety of a New Botulinum Toxin Type A Free of Complexing Proteins

MT10107 is botulinum neurotoxin type A derived drug which utilizes the 150 kDa portion without complexing proteins and human serum albumin contents. To evaluate the efficacy and the safety of MT10107, it was compared with onabotulinumtoxinA in this double-blind, randomized controlled trial. Twenty-five healthy males received a randomly selected dose of MT10107 into the extensor digitorum brevis (EDB) muscle of one foot, and an equivalent dose of onabotulinumtoxinA (BOTOX) was injected into the contralateral EDB muscle. While efficacy of the administered substance was determined by measuring paretic effects on the EDB, the local spread of toxin effects was evaluated by the paretic effects on the nearby abductor hallucis (AH) and abductor digiti quinti (ADQ) muscles. Paretic effects were defined as the percentage of reduction of the compound muscle action potential (CMAP) amplitudes, measured at 14, 30, 90 days after the injection, compared to the baseline value. Intergroup (MT10107 and onabotulinumtoxinA) differences were not significant in the percentage reduction of the amplitudes in the EDB muscles. In this study, there was no significant difference in efficacy and safety between the two test drugs. MT10107 may be effective and safe as much as onabotulinumtoxinA to produce the desired paretic effect.

Determination of Injection Site in Flexor Digitorum Longus for Effective and Safe Botulinum Toxin Injection

Objective To determine the optimal injection site in the flexor digitorum longus (FDL) muscle for effective botulinum toxin injection. Methods Fourteen specimens from eight adult Korean cadavers were used in this study. The most proximal medial point of the tibia plateau was defined as the proximal reference point; the most distal tip of the medial malleolus was defined as the distal reference point. The distance of a line connecting the proximal and distal reference points was defined as the reference length. The X-coordinate was the distance from the proximal reference point to the intramuscular motor endpoint (IME), or motor entry point (MEP) on the reference line, and the Y-coordinate was the distance from the nearest point from MEP on the medial border of the tibia to the MEP. IME and MEP distances from the proximal reference point were evaluated using the raw value and the X-coordinate to reference length ratio was determined as a percentage. Results The majority of IMEs were located within 30%-60% of the reference length from the proximal reference point. The majority of the MEPs were located within 40%-60% of the reference length from the proximal reference point. Conclusion We recommend the anatomical site for a botulinum toxin injection in the FDL to be within a region 30%-60% of the reference length from the proximal reference point.

Management of Severe Bilateral Ptosis in a Patient With Midbrain Infarction: A Case Report

Ptosis could be caused by oculomotor nerve palsy in the midbrain infarction. Bilateral ptosis has been reported in several reports, which focused on clinical characteristics of midbrain infarction. Little research attention has been paid to the treatment of patients with bilateral ptosis in midbrain infarction. We experienced a case of severe bilateral ptosis occurring after midbrain infarction. The patient could not open her eyes, perform basic activities or achieve effective rehabilitation. Neurogenic ptosis can improved after the underlying cause is treated. However, in this case, bilateral ptosis was not improved after conservative care for 6 months and the patient remained limited in activities of daily living and mobility. Surgical correction of bilateral ptosis was done by the resection of both Mullers muscles. After surgical correction, the bilateral ptosis was much improved and the effect persisted for at least 6 months.

Botulinum Toxin for Central Neuropathic Pain

Botulinum toxin (BTX) is widely used to treat muscle spasticity by acting on motor neurons. Recently, studies of the effects of BTX on sensory nerves have been reported and several studies have been conducted to evaluate its effects on peripheral and central neuropathic pain. Central neuropathic pain includes spinal cord injury-related neuropathic pain, post-stroke shoulder pain, multiple sclerosis-related pain, and complex regional pain syndrome. This article reviews the mechanism of central neuropathic pain and assesses the effect of BTX on central neuropathic pain.

Ultrasound Dimensions of the Rotator Cuff and Other Associated Structures in Korean Healthy Adults

In evaluating patients complaining of shoulder pain, ultrasonography is an emerging imaging tool due to convenience, low cost, high sensitivity and specificity. However, normative values of ultrasound dimensions of the shoulder to be compared with pathologic findings in Korean adults are not provided yet. We evaluated the ultrasound dimensions of the rotator cuff, long head of biceps tendon, deltoid muscle and acromioclavicular joint in Korean healthy adults. Shoulder ultrasonography was performed on 200 shoulders from 100 healthy adults. The dimensions of the thickness of rotator cuff (supraspinatus, infraspinatus, subscapularis tendon), deltoid muscle, long head of biceps tendon, subacromial subdeltoid bursa, and acromioclavicular joint interval were measured in a standardized manner. Differences in measurements among sex, age, and dominant arms were compared. The thickness of rotator cuff tendons (supraspinatus, infraspinatus, subscapularis) and deltoid muscle were significantly different between men and women. The thickness of subacromial subdeltoid bursa was significantly different between men and women for non-dominant side. In rotator cuff tendon measurements, the differences between dominant and non-dominant shoulders were not significant, which means the asymptomatic contralateral shoulder can be used to estimate the normal reference values. When stratified by age divided by 10 years, the measurements of supraspinatus, subscapularis and deltoid thickness showed tendency of increase with the age. The acromioclavicular joint interval, on the other hand, revealed decreasing tendency. This report suggests normative values of ultrasound dimensions of healthy Korean population with varying age, and can be useful as reference values in evaluating shoulder pathology, especially in rotator cuff tendon pathology.