Efficacy of botulinum toxin injection before pneumatic dilatation in patients with idiopathic achalasia

Graded pneumatic dilatation (PD) is an appropriate long-term therapy and botulinum toxin injection (BT) is a relatively short-term therapy in idiopathic achalasia. Their combination has not been previously scrutinized. This study aimed to evaluate the role of BT in enhancing the efficacy of PD with 30 mm balloons. Patients who underwent PD with 30 mm balloons after botulinum toxin injections and a group of age- and sex-matched controls who were treated only with PD were enrolled in the study. Symptom scores were taken before, 1 month after and then every 3 months after PD. There were no significant differences between the two groups in gender, duration or severity of symptoms. One of the 12 patients in the case group relapsed 30 months after PD but the others were in remission for an average of 25.6 months. In the control group, all the patients relapsed after a mean of 12.6 months and needed a 35-mm PD. The cumulative remission rate was significantly higher in the case group compared with the control group (P < 0.01). The mean symptom score decreased by 76% in the case group (P < 0.001) and 53% in the controls (P < 0.01) at the end of the first month. Neither age, sex, nor duration or severity of symptoms were predictive of patients' responses to treatment. It seems that BT may be a meaningful enhancing factor in long-term efficacy of PD. PD with a 30 mm balloon after a BT session may resolve the need for the future higher grade PD.     

Modification of Blood Vessel Diameter Following Perivascular Application of Botulinum Toxin-A

The purpose of this study was to demonstrate that perivascularly applied botulinum toxin-A (BTX) increases the diameter of treated blood vessels in a rat femoral vessel exposure model. Six adult Sprague–Dawley rats were used and bilateral femoral artery and vein exposures were performed. Five units of BTX were applied to the experimental side and an equal volume of sterile saline was applied to the control side. Digital images of the vessels were obtained at the following time points: pretreatment, immediately posttreatment, and postoperative days (POD) 1, 14, and 28. Vessel diameters were equivalent at baseline and immediately following application of BTX and saline. The BTX artery was significantly larger than the control artery on POD 1 and 14. The BTX treated artery was significantly larger than all other vessels on POD 14 (p < 0.05) as well as all prior time points (p < 0.01). Direct perivascular application of BTX increases the diameter of rat femoral vessels as early as POD 1. The affect is most robust on POD 14 where the artery was significantly larger than all other vessels at all time points. It is likely that the increased diameter of blood vessels results in an increased blood flow across the area of dilation. Such an increase in flow may serve to improve end-organ perfusion in microvascular procedures.     

Detection of proteinous toxins using the Bio-Threat Alert system, part 3: effects of heat pretreatment and interfering substances

We previously reported that the Guardian Bio-Threat Alert (BTA) system could detect (detection limit: about 0.1 μg/ml) staphylococcal enterotoxin B (SEB), botulinum toxins (BTX) A and B, and ricin, with no interference by white-powdered materials or colored matrices. In this study, the capability of the BTA system was further assessed. With 10 min of preheating at 60°C, all toxins could be detected, but with preheating at 80°C, BTX A and B and ricin became undetectable. About 20% SEB could be detected after heating at 80°C, but this detection ability was completely removed after heating at 100°C. The effects of chemicals usually used for decontamination, such as sodium hypochlorite, hydrogen peroxide, formaldehyde, and sodium nitrite, on the detectability of SEB, BTX A, or ricin in the BTA system were also tested. The concentrations giving 50% line intensity for SEB, BTX A, and ricin were 3.1, 11, and 15 μM for sodium hypochlorite and 88, 210, and 60 mM for formaldehyde, respectively. The addition of hydrogen peroxide or sodium nitrite did not decrease the detectability even when used at high concentrations.     

A cyclic peptide–polymer probe for the detection of Clostridium botulinum neurotoxin serotype A

A Botulinum neurotoxin serotype A (BoNT/A) ELISA detection system was developed based upon an 11-mer cyclic peptide, termed C11-019, that was identified through peptide phage display technology. The assay employs a sandwich format using the C11-019 cyclic peptide attached to a PEMA (poly(ethylene maleic anhydride)) matrix as the capture phase and anti-BoNT/A polyclonal antibodies as the detection phase. Results reported demonstrate that the C11-019 peptide–polymer can specifically bind to BoNT/A with no cross-reactivity to other serotypes examined in assay buffers and a variety of body fluids and foodstuffs. When a highly sensitive chemiluminescent substrate was engaged, the detection of 1 pg/mL could be readily achieved within 3 h with a linear range of 0.1–1 ng/mL. These results demonstrate that an inexpensive peptide–polymer-based capture ELISA system can be used for rapid, sensitive and highly specific BoNT detection.     

Botulinum toxin and neuromotor rehabilitation: An integrated approach to idiopathic cervical dystonia.

Currently, the best treatment option for idiopathic cervical dystonia (ICD) is injection of botulinum toxin (BTX) into the affected muscles, whereas rehabilitative approaches have given disappointing results. We evaluated whether the association of an ad hoc rehabilitative program may improve the clinical efficacy of BTX treatment in a single-center, cross-over, controlled study. Forty patients with ICD were randomly assigned to two different treatment groups: (1) BTX type A (BTX-A) plus a specific program of physical therapy (BTX-PT) or (2) BTX-A alone (BTX-0). Patients in the BTX-PT group showed a longer duration of the clinical benefit (118.8 vs. 99.1 days) and needed a lower dose of BTX at reinjection (284.5 vs. 325.5 units). In addition, they showed more marked reductions in their disability in activities of daily living (-9.7 vs. -4.85 points) and subjective pain (-13.35 vs. 6.95 points) scores. Association of BTX-A therapy with a specific program of physical therapy may improve ICD treatment outcome.     

Isolated high-frequency jaw tremor relieved by botulinum toxin injections.

Jaw tremor can be seen as a component of various neurological disorders such as essential tremor, Parkinson's disease, dystonia, branchial myoclonus, hereditary geniospasm, task-specific tremor, and Whipple's disease, as well as in normal situations such as shivering, and subclinical physiological jaw tremor. In most of these conditions, the jaw tremor is usually associated with tremor or other abnormal involuntary movements affecting additional body parts, and its frequency is lower than 12 Hz. Schrag and colleagues reported a patient with a high-frequency idiopathic jaw tremor, and they speculated it could be related to orthostatic tremor affecting the masseter muscles. We encountered a similar patient with intermittent rapid focal jaw tremor that was successfully treated with botulinum toxin injections to the masseters.     

Treatment of cremaster synkinesias with botulinum toxin A: a video case report.

Synkinesias secondary to nerve lesions and aberrant re-innervation are well-known phenomena especially after lesions of the facial nerve. Synkinesias can successfully be treated with botulinum toxin A (BTx A). Synkinesias of the cremaster muscle have not been described or treated to date. We present the case of a 62-year-old man who developed synkinesias of both cremaster muscles after extensive laparatomy for esophageal cancer. Treatment of synkinesias with various oral medications had been unsuccessful. Electromyography-guided injections of BTx A in both cremaster muscles (15 MU on the right and 10 on the left) led to significant symptom relief for an average of 8 weeks. We present the case including pre- and posttreatment video clips.     

The structure and mode of action of different botulinum toxins

The seven serotypes (A–G) of botulinum neurotoxin (BoNT) are proteins produced by Clostridium botulinum and have multifunctional abilities: (i) they target cholinergic nerve endings via binding to ecto‐acceptors (ii) they undergo endocytosis/translocation and (iii) their light chains act intraneuronally to block acetylcholine release. The fundamental process of quantal transmitter release occurs by Ca²⁺‐regulated exocytosis involving sensitive factor attachment protein‐25 (SNAP‐25), syntaxin and synaptobrevin. Proteolytic cleavage by BoNT‐A of nine amino acids from the C‐terminal of SNAP‐25 disables its function, causing prolonged muscle weakness. This unique combination of activities underlies the effectiveness of BoNT‐A haemagglutinin complex in treating human conditions resulting from hyperactivity at peripheral cholinergic nerve endings. In vivo imaging and immunomicroscopy of murine muscles injected with type A toxin revealed that the extended duration of action results from the longevity of its protease, persistence of the cleaved SNAP‐25 and a protracted time course for the remodelling of treated nerve–muscle synapses. In addition, an application in pain management has been indicated by the ability of BoNT to inhibit neuropeptide release from nociceptors, thereby blocking central and peripheral pain sensitization processes. The widespread cellular distribution of SNAP‐25 and the diversity of the toxin's neuronal acceptors are being exploited for other therapeutic applications.     

Attempts to make models for Alzheimer''s disease

Profound reductions in cortical acetylcholine levels together with degeneration of cholinergic neurons in the basal forebrain have been reported in patients with Alzheimer's disease. A similar loss of the cholinergic neurons of the basal forebrain and impairment of learning and memory occur in animals injected with a nerve growth factor-diphtheria toxin conjugate, suggesting that this animal model is suitable to analyze cholinergic roles on learning and memory processes, and also the pathogenesis of Alzheimer's disease. In addition, animal models constructed by electrolytic or neurotoxic lesioning of the basal magnocellular nucleus, and models made by transgenetic technology were described.