The Usefulness of Swallowing Pressure Assessment in the Identification of Mild Pharyngeal Weakness of Myasthenia Gravis: A Case Report.

Despite the clinical impact of dysphagia in myasthenia gravis (MG), a standard protocol for diagnosing dysphagia reliably has not yet been established. High-resolution manometry (HRM) provides precise information on pharyngeal pressure. We hypothesized that swallowing pressure assessment using HRM during the edrophonium chloride (EC) test could identify mild bulbar symptoms with no abnormalities on videoendoscopic (VE) and videofluorographic (VF) examination of swallowing, and we tested this hypothesis on a 72-year-old female patient diagnosed with ocular MG who developed slight pharyngeal discomfort over 3 months. The patient's ocular symptoms were stable with pyridostigmine medication. VE and VF revealed no abnormalities. The swallowing pressure along the pharynx was measured using HRM during the EC test. HRM parameters, including velopharyngeal contractile integral and meso-hypopharyngeal contractile integral, were evaluated. These parameters were assessed for three swallows using 3 mL of water. After EC injection, the values of the velopharyngeal contractile integral (78.0 ± 5.4 vs. 134.7 ± 1.3 mm Hg cm·s) and the meso-hypopharyngeal contractile integral were both higher (130.6 ± 1.5 vs. 284.2 ± 11.9 mm Hg cm·s) than those observed before EC injection. Chest computed tomography revealed a thymoma that had not been observed in previous examinations. The patient was diagnosed with thymoma-associated MG. Intravenous immunoglobulin therapy improved the mild dysphagia. We concluded that swallowing pressure assessment during the EC test may be helpful in identifying mild bulbar symptoms in patients with MG.

Challenges in diagnosing coexisting ocular myasthenia gravis and thyroid eye disease.

Ocular myasthenia gravis (OMG) and thyroid eye disease are two autoimmune conditions that have several overlapping clinical features, and these coexist with a small but not insignificant frequency. Segregating these diagnoses is typically straightforward, but, when the two diseases co-occur in the same individual, making a diagnosis of OMG can be very challenging. In this review we address what is known about the coexistence of OMG and thyroid eye disease and we highlight the clinical features that are suggestive of overlapping conditions. We also describe the major testing approaches used in the diagnosis of these two entities, with special emphasis on the potential shortcomings of individual tests in patients with overlapping disease. In patients with thyroid eye disease, securing a diagnosis of OMG may not be possible on the basis of a single positive test. A multimodal approach using clinical, serologic, imaging, and electrodiagnostic data, is typically required.

[A case of Miller Fisher syndrome with a false-positive edrophonium test].

A 69-year-old woman presented with acute bilateral ptosis, ophthalmoplegia, ataxia, and hyporeflexia in the extremities following an antecedent upper respiratory infection. We suspected that she had Miller Fisher syndrome (MFS) and performed an edrophonium test (ET) to rule out myasthenia gravis (MG). Edrophonium chloride improved the patient's bilateral ptosis, but not her ophthalmoplegia. Given the absence of the waning phenomenon on electrophysiological examination, the anti-acetylcholine receptor antibody, and a diurnal variation of symptoms, we concluded that the ET result was a false-positive. A diagnosis of MFS was confirmed by the presence of a positive anti-GQ1b antibody. To our knowledge, this is the first case report of MFS with a false-positive ET.

Pharmacological Modulation of Right Ventricular Endocardial-Epicardial Gradients in Brugada Syndrome.

Background We explored the hypothesis that increased cholinergic tone exerts its proarrhythmic effects in Brugada syndrome (BrS) through increasing dispersion of transmural repolarization in patients with spontaneous and drug-induced BrS. Methods BrS and supraventricular tachycardia patients were studied after deploying an Ensite Array in the right ventricular outflow tract and a Cardima catheter in the great cardiac vein to record endo and epicardial signals, respectively. S1-S2 restitution curves from the right ventricular apex were conducted at baseline and after edrophonium challenge to promote increased cholinergic tone. The local unipolar electrograms were then analyzed to study transmural conduction and repolarization dynamics. Results The study included 8 BrS patients (5 men:3 women; mean age, 56 years) and 8 controls patients with supraventricular tachycardia (5 men:3 women; mean age, 48 years). Electrophysiological studies in controls demonstrated shorter endocardial than epicardial right ventricular activation times (mean difference: 26 ms; P<0.001). In contrast, patients with BrS showed longer endocardial than epicardial activation time (mean difference: -15 ms; P=0.001). BrS hearts, compared with controls, showed significantly larger transmural gradients in their activation recovery intervals (mean intervals, 20.5 versus 3.5 ms; P<0.01), with longer endocardial than epicardial activation recovery intervals. Edrophonium challenge increased such gradients in both controls (to a mean of 16 ms [ P<0.001]) and BrS (to 29.7 ms; P<0.001). However, these were attributable to epicardial and endocardial activation recovery interval prolongations in control and BrS hearts, respectively. Dynamic changes in repolarization gradients were also observed across the BrS right ventricular wall in BrS. Conclusions Differential contributions of conduction and repolarization were identified in BrS which critically modulated transmural dispersion of repolarization with significant cholinergic effects only identified in the patients with BrS. This has important implications for explaining the proarrhythmic effects of increased vagal tone in BrS, as well as evaluating autonomic modulation and epicardial ablation as therapeutic strategies.

Reliability and main findings of the flexible endoscopic evaluation of swallowing-Tensilon test in patients with myasthenia gravis and dysphagia.

BACKGROUND AND PURPOSE: Diagnosis of pharyngeal dysphagia caused by myasthenia gravis (MG) based on clinical examination alone is often challenging. Flexible endoscopic evaluation of swallowing (FEES) combined with Tensilon (edrophonium) application, referred to as the FEES-Tensilon test, was developed to improve diagnostic accuracy and to detect the main symptoms of pharyngeal dysphagia in MG. Here we investigated inter- and intra-rater reliability of the FEES-Tensilon test and analyzed the main endoscopic findings. METHODS: Four experienced raters reviewed a total of 20 FEES-Tensilon test videos in randomized order. Residue severity was graded at four different pharyngeal spaces before and after Tensilon administration. All interpretations were performed twice per rater, 4 weeks apart (a total of 160 scorings). Intra-rater test-retest reliability and inter-rater reliability levels were calculated. RESULTS: The most frequent FEES findings in patients with MG before Tensilon application were prominent residues of semi-solids spread all over the hypopharynx in varying locations. The reliability level of the interpretation of the FEES-Tensilon test was excellent regardless of the rater's profession or years of experience with FEES. All four raters showed high inter- and intra-reliability levels in interpreting the FEES-Tensilon test based on residue clearance (kappa = 0.922, 0.981). The degree of residue normalization in the vallecular space after Tensilon application showed the highest inter- and intra-rater reliability level (kappa = 0.863, 0.957) followed by the epiglottis (kappa = 0.813, 0.946) and pyriform sinuses (kappa = 0.836, 0.929). CONCLUSION: Interpretation of the FEES-Tensilon test based on residue severity and degree of Tensilon clearance, especially in the vallecular space, is consistent and reliable.

Diagnosis of Myasthenia Gravis.

Myasthenia gravis (MG) diagnosis is primarily clinically based. By the end of the clinical evaluation, clinicians have a sense as to whether presenting symptoms and elicited signs are weakly or strongly supportive of MG. Diagnostic tests can reaffirm the clinicians' impression. Edrophonium testing is rarely used but helpful in cases of measurable ptosis. Decremental response on slow-frequency repetitive nerve stimulation has a modest diagnostic yield in ocular MG but is helpful in generalized MG cases. The most sensitive test is single-fiber electromyography. In this article, the authors review the diagnostic testing approach of practicing clinicians for suspected MG cases.

Evaluation of the Edrophonium Challenge Test for Cervical Dystonia.

Objective To examine whether or not an edrophonium challenge test is useful for diagnosing cervical dystonia. Patients We evaluated 10 patients with cervical dystonia and 10 with hemifacial spasms (disease controls). We administered edrophonium and saline in this double-blinded study. Before and after the injection, we recorded the participants' clinical signs using a video camera to assess the objective symptoms every two minutes. Ten minutes after the saline and edrophonium injections, participants evaluated their subjective clinical signs using a visual analog scale. The objective signs on the video recordings were scored by specialists who were blinded to the treatment. The mean visual analog scale scores were compared using the Wilcoxon rank-sum test for paired continuous variables. Results The clinical signs of participants with cervical dystonia were amplified by edrophonium. In contrast, the clinical signs in participants with hemifacial spasms were not affected by the edrophonium challenge test. Conclusion The edrophonium challenge test may be useful for diagnosing cervical dystonia.

Detectable voice change with the edrophonium test in laryngeal myasthenia gravis.

A case of laryngeal myasthenia gravis in a 65-year-old woman presenting with hoarseness as the sole symptom is reported. Voice spectrography was performed before and after injection of intravenous edrophonium. There was a marked improvement in the patient's voice after the administration of edrophonium, which was confirmed by the changes seen on the sound spectrogram. This was the only objective indication of a diagnosis of myasthenia gravis. No thymoma was seen on chest X-ray and the patient was negative for anti-acetylcholine receptor antibodies. Treatment for laryngeal myasthenia gravis was initiated and the patient's vocal problems resolved. This case emphasizes the need to consider systemic diseases in the differential diagnosis of hoarseness and demonstrates the need for careful follow-up in such patients.

Bulbar Myasthenia Gravis Superimposed in a Medullary Infarction Diagnosed by a Fiberoptic Endoscopic Evaluation of Swallowing With Simultaneous Tensilon Application.

In the elderly, myasthenia gravis (MG) can present with bulbar symptoms, which can be clinically difficult to diagnose from other neurological comorbid conditions. We describe a case of a 75-year-old man who had been previously diagnosed with dysphagia associated with medullary infarction but exhibited aggravation of the dysphagia later on due to a superimposed development of bulbar MG. After recovering from his initial swallowing difficulties, the patient suddenly developed ptosis, drooling, and generalized weakness with aggravated dysphagia. Two follow-up brain magnetic resonance imaging (MRI) scans displayed no new brain lesions. Antibodies to acetylcholine receptor and muscle-specific kinase were negative. Subsequent electrodiagnosis with repetitive nerve stimulation tests revealed unremarkable findings. A diagnosis of bulbar MG could only be established after fiberoptic endoscopic evaluation of swallowing (FEES) with simultaneous Tensilon application. After application of intravenous pyridostigmine, significant improvement in dysphagia and ptosis were observed both clinically and according to the FEES.

Bulbar Myasthenia Gravis Superimposed in a Medullary Infarction Diagnosed by a Fiberoptic Endoscopic Evaluation of Swallowing With Simultaneous Tensilon Application

In the elderly, myasthenia gravis (MG) can present with bulbar symptoms, which can be clinically difficult to diagnose from other neurological comorbid conditions. We describe a case of a 75-year-old man who had been previously diagnosed with dysphagia associated with medullary infarction but exhibited aggravation of the dysphagia later on due to a superimposed development of bulbar MG. After recovering from his initial swallowing difficulties, the patient suddenly developed ptosis, drooling, and generalized weakness with aggravated dysphagia. Two follow-up brain magnetic resonance imaging (MRI) scans displayed no new brain lesions. Antibodies to acetylcholine receptor and muscle-specific kinase were negative. Subsequent electrodiagnosis with repetitive nerve stimulation tests revealed unremarkable findings. A diagnosis of bulbar MG could only be established after fiberoptic endoscopic evaluation of swallowing (FEES) with simultaneous Tensilon application. After application of intravenous pyridostigmine, significant improvement in dysphagia and ptosis were observed both clinically and according to the FEES.

Edrophonium Challenge Test for Blepharospasm.

BACKGROUND: Blepharospasm is typically diagnosed by excluding any secondary diseases and neuropsychiatric disorders, as specific tests for blepharospasm are currently unavailable. Since anticholinergic agents are used to improve the symptoms of dystonia, we hypothesized that edrophonium chloride, an acetylcholinesterase inhibitor, may make the symptoms of dystonia more apparent. Therefore, we examined whether an edrophonium challenge test would be useful for diagnosing blepharospasm. METHODS: We studied 10 patients with blepharospasm and 10 with hemifacial spasms (as disease controls). We administered edrophonium and saline in this double-blind study. Before and after the injection, we recorded the clinical signs using a video camera to assess the objective symptoms every 2 min. Ten minutes after the isotonic sodium chloride and edrophonium injections, the patients evaluated their subjective signs using a visual analog scale (VAS). The objective signs on the video recordings were scored by specialists who were blind to the treatment. RESULTS: The subjective and objective signs of the patients with blepharospasm were amplified by edrophonium. In contrast, the signs in patients with hemifacial spasms were not changed by the edrophonium challenge test. CONCLUSIONS: The edrophonium challenge test may be used to diagnose blepharospasm. The study was registered with a ICMJE recognized registry, the UMIN-CTR, with the number UMIN000022557.

Reversal of neuromuscular block in companion animals.

OBJECTIVE: To review the evidence regarding the reversal of neuromuscular block (NMB) in companion animals with emphasis on the development and use of newer agents. DATABASE USED: Data sources include scientific reviews and original research publications in both human and veterinary literature using Pubmed and Scopus as search data bases. Unpublished and locally published data on reversal of NMB are presented. CONCLUSIONS: Residual NMB has been shown to increase morbidity and mortality in humans and needs to be avoided. It can be detected only by adequate neuromuscular monitoring. The proper use of reversal agents avoids residual NMB and recurarization should not occur. Anticholinesterase inhibitors, such as edrophonium and neostigmine have been used to reverse NMB when the need for this has been established. Reversal is influenced by several factors and a number of undesirable side- effects of these drugs have been reported. Sugammadex, a γ-cyclodextrin, which was designed specifically to encapsulate rocuronium, is more rapid in its actions, has fewer side effects and can reverse profound NMB induced by aminosteroidal muscle relaxants.

Effects of Anticholinesterases on Catalysis and Induced Conformational Change of the Peripheral Anionic Site of Murine Acetylcholinesterase.

Conventional insecticides targeting acetylcholinesterase (AChE) typically show high mammalian toxicities and because there is resistance to these compounds in many insect species, alternatives to established AChE inhibitors used for pest control are needed. Here we used a fluorescence method to monitor interactions between various AChE inhibitors and the AChE peripheral anionic site, which is a novel target for new insecticides acting on this enzyme. The assay uses thioflavin-T as a probe, which binds to the peripheral anionic site of AChE and yields an increase in fluorescent signal. Three types of AChE inhibitors were studied: catalytic site inhibitors (carbamate insecticides, edrophonium, and benzylpiperidine), peripheral site inhibitors (tubocurarine, ethidium bromide, and propidium iodide), and bivalent inhibitors (donepezil, BW284C51, and a series of bis(n)-tacrines). All were screened on murine AChE to compare and contrast changes of peripheral site conformation in the TFT assay with catalytic inhibition. All the inhibitors reduced thioflavin-T fluorescence in a concentration-dependent manner with potencies (IC50) ranging from 8 nM for bis(6)-tacrine to 159 µM for benzylpiperidine. Potencies in the fluorescence assay were correlated well with their potencies for enzyme inhibition (R2 = 0.884). Efficacies for reducing thioflavin-T fluorescence ranged from 23-36% for catalytic site inhibitors and tubocurarine to near 100% for ethidium bromide and propidium iodide. Maximal efficacies could be reconciled with known mechanisms of interaction of the inhibitors with AChE. When extended to pest species, we anticipate these findings will assist in the discovery and development of novel, selective bivalent insecticides acting on AChE.

Upper eyelid retraction disclosed after edrophonium chloride administration in a patient with Graves' orbitopathy and myasthenia gravis.

Patients with Graves' orbitopathy have a higher probability of myasthenia gravis than does the normal population. Overlapping clinical features cause diagnostic confusion in such a situation. We herein report a patient with Graves' orbitopathy and myasthenia gravis (GO-MG) with normal left eyelid height, but in whom upper eyelid retraction was shown after edrophonium chloride administration. Upper eyelid retraction in GO-MG is occasionally masked by a myasthenia effect. The upper eyelid height must be carefully monitored in patients with Graves' orbitopathy to detect the presence of concomitant myasthenia gravis.

Effects of Edrophonium and/or Pseudocholinesterase for the Reversal of Mivacurium-Induced Paralysis in vitro / 대한마취과학회지

BACKGROUND: Mivacurium is a nondepolarizing neuromuscular blocking agent hydrolyzed by pseudocholinesterase. Anticholinesterase used in the reversal of mivacurium-induced muscle relaxation may also inhibit plasma pseudocholinesterase, and delay hydrolysis of mivacurium. In this study, the effects of edrophonium and/or bovine pseudocholinesterase (BpChE) in the reversal of mivacurium were investigated with the rat phrenic nerve-diaphragm preparation. METHODS: Fifty Sprague-Dawley rats (150 - 200 g) were randomly allocated into 10 groups based on the dosage of edrophonium and BpChE. Each animal was anesthetized with thiopental sodium (40 mg/kg I.P.). The phrenic nerve-diaphragm was dissected and mounted in a bath containing an oxygenated Krebs' solution at 32degreesC. The phrenic nerve was stimulated at supramaximal intensity and the single twitch responses and train of four (TOF) ratio were measured. After stabilization of the twitch responses, mivacurium (1ng/ml) was administered incrementally to obtain more than 95% twitch inhibition. Reversal of the mivacurium-induced block by edrophonium (0.01, 0.1, 1, or 10ng/ml) and/or BpChE (0.1 u, or 1.0 u/ml) were tested. A single twitch height more than 75% of the baseline value was considered an adequate reversal. RESULTS: Mivacurium-induced paralysis was recovered more effectively by BpChE 1.0 u/ml than the other groups. Edrophonium improved a single twitch in a dose dependent manner. CONCLUSIONS: Mivacurium-induced paralysis can be more effectively reversed by BpChE than edrophonium. Inhibition of pseudocholinesterase was not observed by increasing the dose of edrophonium.

The Effect of 4-Aminopyridine with Anticholinesterases on MgSO4-Rocuronium-Induced Neuromuscular Blockade in Vitro / 대한마취과학회지

BACKGROUND: The aim of this study was to evaluate the effect of 4-aminopyridine (4-AP) combined with anticholiesterase (antiChE) in antagonizing MgSO4-rocuronium-induced neuromuscualr blockade using a rat hemidiaphragm. METHODS: A hemidiaphragm with phrenic nerve was dissected and was mounted in a bath containing oxygenated Krebs solution. The phrenic nerve was stimulated supramaximally and the twitch response (0.1 Hz) was stabilized for at least 30 minutes. After maximal twitch inhibition by IC95 (concentration of 95% twitch inhibition) of rocuronium and MgSO4 20 mg was achieved, antagonistic effects of 1.6, 16 microgram/ml of edrophonium, 0.1, 1.0 microgram/ml of neostigmine, 0.5, 5.0 microgram/ml of pyridostigmine, and 0.8 microgram/ml of 4-AP combined with each of the above mentioned antiChEs were investigated. RESULTS: Whereas antiChE alone at low concentration partially recovered only the twitch response, 4-AP combined with antiChE recovered both the twitch and train-of-four responses significantly. CONCLUSIONS: 4-AP enhances antagonism of a magnesium-rocuronium induced neuromuscular blockade by edrophonium, neostigmine or pyridostigmine in vitro.

The Effect of Selective Muscarinic Receptor Antagonists on Antiallodynic Action in a Rat Model of Neuropathic Pain / 대한마취과학회지

BACKGROUND: Peripheral nerve injury may produce a syndrome consisting of spontaneous pain, allodynia and hyperpathia. In previous study, we examined the antiallodynic action produced by intrathecal (i.t.) cholinesterase inhibitors (ChEi) in a neuropathic pain rat model and the reversal of antiallodynic state by i.t. atropine, muscarinic antagonist, but not by nicotinic antagonist mecamylamine. The purpose of this study was to determine the selective antagonistic action of four subtypes of muscarinic receptor on antiallodynic state by i.t. ChEi in a rat model of neuropathic pain. METHODS: Sprague Dawley rats were prepared with tight ligation of left L5/L6 spinal nerves with 6-0 black silk and chronic lumbar intrathecal catheters. After obtaining the baseline hindpaw withdrawal scores, edrophonium (100 microgram) or neostigmine (10 microgram) was administered intrathecally. Tactile allodynia was measured using von Frey filaments and allodynic threshold was calculated by the up-down method. Allodynic changes were tested at 15, 30, 45, 60, 90, 120 and 180 minutes. To examine the reversal of antiallodynia and to compare the antagonizing action of antiallodynic state produced by i.t. administration of ChEi, non-selective muscarinic receptor antagonists atropine (10 microgram), M1 antagonist pirenzepine (3 microgram), M2 antagonist methoctramine (3 microgram), M3 antagonist 4-DAMP (3 microgram) and M4 antagonist tropicamide (3 microgram) were injected intrathecally respectively 5 minutes prior to the injection of edrophonium or neostigmine. RESULTS: Antiallodynia produced by i.t. edrophonium was reversed by pretreatment with i.t. methoctramine, 4-DAMP, tropicamide and pirenzepine (P<0.05). On the contrary, antiallodynic state made by i.t. neostigmine was not antagonized by methoctramine, 4-DAMP and tropicamide. M1 antagonist pirenzepine had a moderate, statistically significant (P<0.05) effect on reversal of increased allodynic threshold while atropine showed a complete antagonism. CONCLUSION: These experiments suggest that antialllodynic action of cholinesterase inhibitors is likely due to mediation of spinal muscarinic system and M1 receptor subtype is more likely involved in this mechanism.

Reversal Effects of Neostigmine, Edrophonium and 4-aminopyridine of Verapamil Pretreatment on Pipecuronium Induced Neuromuscular Blockade in Rat-Hemidiaphragm / 대한마취과학회지

BACKGROUND: It has been shown that L-type calcium channel blockers increase the muscle relaxation effects of non-depolarizing neuromuscular blocking agents whereas the potentiated neuromuscular blocking effects by L-type calcium channel blocker are resistant to reversal by neostigmine. The aims of this study were 1) to see whether the pretreatment of L-type calcium channel blocker, such as verapamil, aggravates the pipecuronium-induced muscle relaxation, 2) if so, to see whether these effects are reversed by anticholinesterase, such as neostigmine and edrophonium or potassium channel blocker, such as 4-aminopyridine. METHODS: The rat-phrenic nerve-hemidiaphragms (n=60) were prepared. Twenty microgram of pipecuronium was administered to all organ bath. All samples were divided into two groups according to the administration of 10uM of verapamil i.e. verapamil pretreated, non-pretreated group. The amounts of administered pipecuronium were gradually increased by 4ug until the force of twitch decreased to 10% of control value in both groups. Each group was subdivided into three groups according to the administration of 0.75 M of neostigmine, 12.4 uM of edrophonium or 40uM of 4-aminopyridine. RESULTS: The dose of pipecuronium required for the decrease of contractile force to 10% of control value was less in verapamil pretreated group than in non-pretreated group. And, the decrease of contractile force in both groups was more effectively reversed by 4-aminopyridine than neostigmine and edrophonium. CONCLUSIONS: Verapamil potentiates the pipecuronium-induced neuromuscular blockade and 4-aminopyridine is more effective to reverse verapamil pretreated, pipecuronium induced neuromuscular blockade.

The Antiallodynic Effect of Edrophonium and Neostigmine in a Neuropathic Pain Model / 대한마취과학회지

BACKGROUND: Peripheral nerve injury may produce a syndrome consisting of spontaneous pain, allodynia and hyperpathia. Cholinesterase inhibitors are known to have an antinociceptive effect in hot plate and tail flick tests and to be mediated by spinal muscarinic system. The purpose of the current study was to determine the effect of intrathecally (i.t.) administered edrophonium and neostigmine on the touch-evoked allodynia and to identify the antagonism of antiallodynia in a rat model of neuropathic pain. METHODS: Sprague Dawley rats were prepared with tight ligation of left L5/L6 spinal nerves with 6~0 black silk and chronic lumbar intrathecal catheters. After obtaining the baseline hindpaw withdrawal scores, edrophonium (3~100ug) or neostigmine (0.3~10ug) was administered intrathecally. Tactile allodynia was measured using von Frey filaments and allodynic threshold was calculated by updown method. Motor dysfunction was assessed by observing righting/stepping reflex responses and abnormal weight bearing. To examine the reversal of antiallod ynia, muscarinic receptor antagonist atropine (10ug) or nicotinic receptor antagonist mecamylamine (10ug) was injected intrathecally 5 min. prior to injection of edrophonium or neostigmine. RESULTS: I.t. edrophonium and i.t. neostigmine produced a dose dependent antagonism of allodynic state but had moderate to severe effect on motor weakness at doses of 3 and 10 g of neostigmine. Pretreatment with i.t. atropine yielded a complete antagonism of antiallodynia in both drugs, but i.t. mecamylamine did not significantly reverse incresed allodynic threshold. CONCLUSIONS: These experiments suggest that i.t. edrophonium or i.t. neostigmine produces a dose dependent antagonism on touch-evoked allodynia at the spinal level and this antagonism is likely due to spinal muscarinic system.

Origem esofágica de dor precordial em pacientes chagásicos com artérias coronárias subepicárdicas normais / Esophageal origin of precordial pain in chagasic patients with normal subepicardial coronary arteries

PURPOSE--To study the chest pain of esophageal origin in chagasic patients (CH) and non-chagasic subjects (NCH) with normal coronary arteries. METHODS--The study comprised 48 patients: 33 CH (age 56 years, 50 male) and 15 NCH (age 47 years, 25 male), with precordial chest pain and normal subepicardial coronary arteries. They were assigned to upper digestive tract radiologic and endoscopic study, esophageal manometric evaluation at baseline and after provocative tests (Bernstein and intravenous edrophonium). RESULTS--Radiologic study: 14 (42) CH and 4 (27) NCH had esophageal dilation (p > 0.05). Hiatal hernia was documented in 7 (21) CH and 6 (40) NCH (p > 0.05). 2) Digestive endoscopy: In 15 (45) CH and 6 (40) NCH distal esophagitis were seen. In the NCH, esophagitis occurred with hiatal hernia; however only 30 of CH with esophagitis had also hiatal hernia while another 30 had esophageal dilation. 3) Esophageal motility disorders (EMD): 11 (33) CH showed EMD--8 with inferior esophageal sphincter achalasia (IESA) and 3 with diffuse esophageal spasm. Among NCH, 2 (13) had IESA (p > 0.05). 4) Bernstein test--a positive test was seen in 5 (15) CH and 3 (20) NCH-p > 0.05. CH with esophageal dilation had 14 of positive results, while CH without esophageal dilation had 16-p > 0.05. 5) Intravenous edrophonium-esophageal contraction amplitude enhancement provoked by the drug infusion was clearly attenuated in the chagasic (6.9 +/- 12.7 mmHg) when compared with the NCH group (18.8 +/- 21.4 mmHg). A positive test (i.e. chest pain) was obtained in only one patient who was NCH. CONCLUSION--Esophageal pain could be elicited at a relatively low and comparable rate in both groups of patients.