Comprehensive Use of Dynamic Electrical Neurostimulation and Botulinum Toxin Therapy in Patients with Post-Stroke Spasticity.

BACKGROUND: Acute cerebrovascular accident poses a threat to the health of the nation. Dynamic electric neurostimulation decreases the excitability of the receptor apparatus, optimize microcirculatory processes, analgesic and antispasmodic effects. METHODS: This article discusses the rehabilitation of 96 men and women with post-stroke spasticity, mean age of 60.51 ± 4.9 years, in the early recovery period after ischemic stroke, randomized into 4 equal groups: Group 1 received botulinum toxin therapy in combination with dynamic electric neurostimulation and basic therapy, including massage and therapeutic exercises; Group 2 -botulinum toxin therapy and basic therapy; Group 3 - dynamic electric neurostimulation and basic therapy; Group 4 - basic therapy only. Study methods included the use of the Modified Asworth Scale to assess spasticity, the Rivemead Motor Assessment test, and goniometry to assess the range of joint movements. RESULTS: During a three-week observation, it was found that the inclusion of botulinum toxin therapy and dynamic electrical neurostimulation in the standard therapy of post-stroke spasticity in patients after ischemic stroke in the early recovery period contributed to patients' recovery. CONCLUSIONS: Botulinum toxin therapy and dynamic electrical neurostimulation contributed to a more significant decrease in spasticity in the proximal and distal parts of the paretic upper extremity. It is also increased the amplitude of voluntary movements in the affected shoulder, elbow, and wrist joints, compared to the separate use of botulinum toxin therapy and dynamic electric neurostimulation as part of basic rehabilitation.

Rho as a target to promote repair: translation to clinical studies with cethrin.

Spinal cord injury (SCI) often results in permanent paralysis because there is little spontaneous repair. Neuronal injury in the central nervous system (CNS) causes breakage of axonal connections, release of myelin, inflammation and cell death at the lesion site. Many factors contribute to the failure of spontaneous repair after SCI, including the presence of growth inhibitory proteins in myelin, the inflammatory environment of the injured CNS, and the resulting signaling cascades that result in over-activation of Rho, a signaling switch in neurons and axons. In this review, we provide a general overview of growth inhibition in the CNS, and show evidence that most growth inhibitory proteins signal through a common intracellular pathway. Rho is a convergent signal for growth inhibition, and also for signaling some of the secondary consequences of inflammation after SCI. We review the preclinical evidence that targeting Rho is an effective way to stimulate axon regeneration and functional recovery in preclinical animal models. In the last part of the review, we describe the creation of Cethrin, a new investigational drug, and summarize the results of the Phase I/IIa clinical study to examine the safety, tolerability and efficacy of Cethrin in patients with acute SCI. We conclude with some insight for future clinical studies.

A botulinum neurotoxin-like function of Potentilla chinensis extract that inhibits neuronal SNARE complex formation, membrane fusion, neuroexocytosis, and muscle contraction.

CONTEXT: Botulinum neurotoxins (BoNTs) are popularly used to treat various diseases and for cosmetic purposes. They act by blocking neurotransmission through specific cleavage of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Recently, several polyphenols were shown to interfere with SNARE complex formation by wedging into the hydrophobic core interface, thereby leading to reduced neuroexocytosis. OBJECTIVE: In order to find industrially-viable plant extract that functions like BoNT, 71 methanol extracts of flowers were screened and BoNT-like activity of selected extract was evaluated. MATERIALS AND METHODS: After evaluating the inhibitory effect of 71 flower methanol extracts on SNARE complex formation, seven candidates were selected and they were subjected to SNARE-driven membrane fusion assay. Neurotransmitter release from neuronal PC12 cells and SNARE complex formation inside the cell was also evaluated. Finally, the effect of one selected extract on muscle contraction and digit abduction score was determined. RESULTS: The extract of Potentilla chinensis Ser. (Rosaceae)(Chinese cinquefoil) flower inhibited neurotransmitter release from neuronal PC12 cells by approximately 90% at a concentration of 10 µg/mL. The extract inhibited neuroexocytosis by interfering with SNARE complex formation inside cells. It reduced muscle contraction of phrenic nerve-hemidiaphragm by approximately 70% in 60 min, which is comparable to the action of the Ca²âº-channel blocker verapamil and BoNT type A. DISCUSSION AND CONCLUSION: While BoNT blocks neuroexocytosis by cleaving SNARE proteins, the Potentilla chinensis extract exhibited the same activity by inhibiting SNARE complex formation. The extract paralyzed muscle as efficiently as BoNT, suggesting the potential versatility in cosmetics and therapeutics.

Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials.

BACKGROUND: Few evidence-based treatment guidelines for tendinopathy exist. We undertook a systematic review of randomised trials to establish clinical efficacy and risk of adverse events for treatment by injection. METHODS: We searched eight databases without language, publication, or date restrictions. We included randomised trials assessing efficacy of one or more peritendinous injections with placebo or non-surgical interventions for tendinopathy, scoring more than 50% on the modified physiotherapy evidence database scale. We undertook meta-analyses with a random-effects model, and estimated relative risk and standardised mean differences (SMDs). The primary outcome of clinical efficacy was protocol-defined pain score in the short term (4 weeks, range 0-12), intermediate term (26 weeks, 13-26), or long term (52 weeks, ≥52). Adverse events were also reported. FINDINGS: 3824 trials were identified and 41 met inclusion criteria, providing data for 2672 participants. We showed consistent findings between many high-quality randomised controlled trials that corticosteroid injections reduced pain in the short term compared with other interventions, but this effect was reversed at intermediate and long terms. For example, in pooled analysis of treatment for lateral epicondylalgia, corticosteroid injection had a large effect (defined as SMD>0·8) on reduction of pain compared with no intervention in the short term (SMD 1·44, 95% CI 1·17-1·71, p<0·0001), but no intervention was favoured at intermediate term (-0·40, -0·67 to -0·14, p<0·003) and long term (-0·31, -0·61 to -0·01, p=0·05). Short-term efficacy of corticosteroid injections for rotator-cuff tendinopathy is not clear. Of 991 participants who received corticosteroid injections in studies that reported adverse events, only one (0·1%) had a serious adverse event (tendon rupture). By comparison with placebo, reductions in pain were reported after injections of sodium hyaluronate (short [3·91, 3·54-4·28, p<0·0001], intermediate [2·89, 2·58-3·20, p<0·0001], and long [3·91, 3·55-4·28, p<0·0001] terms), botulinum toxin (short term [1·23, 0·67-1·78, p<0·0001]), and prolotherapy (intermediate term [2·62, 1·36-3·88, p<0·0001]) for treatment of lateral epicondylalgia. Lauromacrogol (polidocanol), aprotinin, and platelet-rich plasma were not more efficacious than was placebo for Achilles tendinopathy, while prolotherapy was not more effective than was eccentric exercise. INTERPRETATION: Despite the effectiveness of corticosteroid injections in the short term, non-corticosteroid injections might be of benefit for long-term treatment of lateral epicondylalgia. However, response to injection should not be generalised because of variation in effect between sites of tendinopathy. FUNDING: None.

Diagnostic use of botulinum toxin in patients with Duane syndrome.

INTRODUCTION: Duane syndrome is a difficult condition to treat. Patients and parents need to be informed that it will not resolve and it is not possible to create normal eye movements surgically. Botulinum toxin may be used to assess the likelihood of reducing the abnormal head posture and reducing the diplopia by increasing the field of binocular single vision. If results are favorable then surgery may be offered. This article is a retrospective review of patients with Duane syndrome treated with botulinum toxin using the toxin clinic database between 1980 and 2007. METHODS: Eighty-eight patients were identified, 48 females and 40 males. The average age at presentation was 29 years, range 5 to 68 years. The left eye was affected in 50 (57%) patients and 21 (24%) patients were affected bilaterally. The average angle was 28.6 +/- 18.4 Delta for the esotropic patients and 32.5 +/- 14.5 Delta for the exotropic patients. In 58 patients the medial rectus was injected, in 30 the lateral rectus. RESULTS: As a result of the outcome of botulinum toxin, 41 (46.5%) patients proceeded to surgery; 12 (14%) continued with maintenance toxin. Forty-seven (53%) demonstrated a long-term reduction in deviation. Transient complications were ptosis in 11 patients and induced vertical deviation in 10. CONCLUSION: This is the first study to explore the diagnostic role of botulinum toxin in Duane syndrome. It is a safe treatment that may also offer long-term benefits.

Botulinum toxin: new option for refractory lower urinary tract symptoms in women.

Lower urinary tract symptoms refractory to standard therapies create significant distress and quality of life impact for women with these disorders. Likewise, they are challenging for clinicians caring for these women. Once conservative measures are exhausted, the few remaining treatment options are often invasive and associated with significant morbidity. Botulinum toxin is an emerging medical therapy with increasing applications in the lower urinary tract and pelvic floor, which has proven to be an effective and safe alternative for the treatment of some refractory pelvic floor disorders.

Botulinum toxin type-B improves sialorrhea and quality of life in bulbaronset amyotrophic lateral sclerosis.

BACKGROUND: Sialorrhea is a disabling problem in bulbaronset amyotrophic lateral sclerosis (ALS). Botulinum toxin (BTX) type A and B have been proposed as alternatives to traditional treatments. OBJECTIVES: To evaluate the efficacy and safety of BTX type B in the treatment of sialorrhea in patients with bulbar-onset ALS. METHODS: Open-label prospective study of BTX type B injections in parotids (1000 U) and submandibular (250 U) glands using anatomic landmarks. Primary outcome was rate of responders (improvement > 50% on visual analogue scales (VAS) of severity and disability of sialorrhea) 1 month post-treatment. Other outcomes included subjective (drooling and quality of daily living questionnaires) and objective (cotton roll weights and number of paper handkerchiefs used) evaluations. Safety evaluations included questionnaires regarding brain stem symptoms. RESULTS: Sixteen ALS patients were included. At 1 month the rate of responders was 75% with a mean reduction of 70% in severity and disabling VASs. Fifteen patients (94 %) reported some benefit with drooling reduction. In objective measurements there was a reduction over 60 % in saliva production and in the number of handkerchiefs used. Onset of effect occurred within 3 days. Most patients reported better quality of living. The most frequent side-effects were viscous saliva, local pain, chewing weakness and respiratory infection. There were no changes in blood pressure or cardiac rate. At 3 months, there was still a positive effect in all outcomes. All patients except one manifested their willingness to repeat treatment. CONCLUSIONS: Anatomic guided BTX type B injections seem effective and safe to treat sialorrhea in bulbar-onset ALS.

Botulismo y toxina botulínica / Botulism and botulinum toxin

El botulismo es una toxi-infección producida por la bacteria anaerobia Clostridium botulinum por medio de una potentísima toxina, la toxina botulínica, de la cual existen ocho serotipos diferentes. Ésta es capaz de provocar en humanos al menos cuatro cuadros clínicos diferentes por bloqueo de la transmisión neuromuscular, y que pueden variar en gravedad desde la casi ausencia de síntomas hasta la muerte por parálisis respiratoria. Paradójicamente, la toxina botulínica se presenta también como un arma terapéutica eficaz y segura en decenas de enfermedades, si bien gran parte de estas potenciales aplicaciones está aún en fase de investigación. (AU)

Short-term electrical stimulation enhances the effectiveness of Botulinum toxin in the treatment of lower limb spasticity in hemiparetic patients.

The study tested the spasmolytic effect of Botulinum toxin A in two groups of hemiparetic patients with lower limb spasticity: in the first group (n = 5) 2000 U Dysport were injected into the soleus, tibialis posterior and both heads of gastrocnemius muscles alone; the second (n = 5) received additional repetitive alternating electrical stimulation of M. tibialis anterior and plantar flexors for 30 min six times per day during the 3 days following the injection. Muscle tone, rated by the Ashworth spasticity score, and gait analysis including recording of vertical ground reaction forces, were assessed before and 4 weeks after injection. The combined treatment proved to be more effective with respect to the clinically assessed reduction of muscle tone, gait velocity, stride length, stance- and swing-symmetry (P < 0.05). The result is discussed with reference to animal experiments demonstrating enhanced toxin uptake and accelerated onset of its paralytic effect by electrical stimulation.

Click-evoked vestibulocollic reflexes in torticollis.

A total of 26 patients with torticollis were studied using a recently developed technique for recording vestibulocollic reflexes from the sternocleidomastoid muscles in addition to conventional caloric tests of vestibular function. Previous reports of abnormalities of vestibulo-ocular reflexes in these patients were confirmed with just fewer than half having significant canal pareses or directional preponderances (nine of 20 tested). In addition, there was a high incidence of abnormal click-evoked vestibulocollic reflexes (17 of 26 tested), which were not simply the result of prior treatment with botulinum toxin, nor due to unequal levels of muscle activation. In patients never previously treated with botulinum toxin (14 patients), the effect almost always consisted of suppressed responses in the sternocleidomastoid muscle ipsilateral to the direction of head turning. Because responses were not abnormal in all patients tested, and more commonly so in those with a history of torticollis of > or = 5 years (eight of nine patients) than in de novo patients, we suggest that the changes are more likely to be compensatory than causal.