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.

Ice-on-Eyes Test in the Diagnosis of Myasthenia Gravis.

Myasthenia gravis is the most frequent autoimmune neuromuscular transmission disorder with incidence of 2-20 patients per million. Its pathophysiology is autoimmune, with acetylcholine receptor auto antibodies damaging the post-synaptic fold at the muscle membrane. The diagnostic confirmation of myasthenia gravis is often challenging. Ice-oneyes test can be used to diagnose this disease for its simplicity, safety and cost-effectiveness. Here we report a case of myasthenia gravis in Enam Medical College Hospital, Savar, Dhaka where ice-on-eyes test was done with improvement of ptosis of the patient. Aim of this case report is to make aware our physicians to apply this simple bed side test instead of common traditional edrophonium (tensilon test) test for confirmation of the diagnosis of ocular 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.

Comparative study of edrophonium test and neostgmine test in ocular myasthenia gravis.

To compare the sensitivity of edrophonium test and neostigmine test in ocular myasthenia. Materials and methods: the edrophonium and neostimine tests in 57 consecutive patients who presented with symptoms of ptosis and/or binocular diplopia upon exertion were studied prospectively in Neuroophthalmologic Unit, Siriraj Hospital. The palpebral fissure, marginal reflex distance (MRD), levator palpebare superioris muscle function and angle of deviation by Prism and cover test were measured before and after performing the tests for evaluation of positive result of the edrophonium and neostigmine tests. All patients were treated with pyridostigmine for one week. The patients who responded to the treatment were diagnosed as ocular myasthenia gravis. Statistical analysis was carried out by the Chi-square test. Results: Forty-five patients were diagnosed as ocular myasthenia gravis and 12 patients were nonmyasthenic group. The edrophonium test was positive in 44 patients (97.8%) and the neostigmine test was positive in 38 patients (84.4%) in myasthenic group. In nonmyasthenic group, 12 patients (100%) were found negative in both tests. Edrophonium produced more severe side effects than neostigmine. Conclusion: The neostigmine test displayed similar positive result compared with the edrophonium test but is safer and easier to perform.

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.

Effects of Neostigmine , Pyridostigmine and Edrophonium on Plasma Cholinesterase Activity and Train-of-four Response / 대한마취과학회지

Effects of the anticholinesterase drugs on plasma cholinesterase activity, plasma albumin level and train-of-four response were investigated in 38 ASA class 1 or 2 adult patients undergoing elective surgery. Anesthesia was induced with thiopental sodium 5~6 mg/kg followed by succinylcholine 1 mg/kg to facilitated tracheal intubation, and was maintained with O2-N2O(50%)-enflurane (1~2%). For maintenance of adequate muscle relaxation, initial bolus (0.08 mg/kg) and small incremental doses (0.02~0.04 mg/kg) of vecuronium were administered. At the end of surgery, neuromuscular blockade was reversed with neostigmine 0.04 mg/kg as a single bolus dose (neostigmine group, n=10), divide dose of neostigmine (20%:80%, neostigmine-divide group, n=10), pyridostigmine 0.2mg/kg (pyridostigmine group, n=10), or edrophonium 0.5mg/kg (edrophonium group, n=8) respectively. Reversal was attempt at 10% spontaneous recovery of first twitch height (T1), which was measured using train-of-four (TOF) stimulation of ulnar nerve repeated every 20 seconds (EMG, Datex co.). The results obtained were as follows: 1) Neostigmine, neostigmine-divide and pyridostigmine groups all produced markedly inhibition of plasma cholinesterase activity which was maximum at 5 minutes after injection, and was persisted significantly for 60 miuntes in both neostigmine and neostigmine-divide groups, and for 120 minutes in pyridostigmine group. The inhibition of plasma cholinesteraae was correlated significantly with TOF recovery in all groups except in edrophonium group. There was no inhibition of enzymatic activity up to 30 minutes in edrophonium group. 2) The changes in plasma albumin level after administration of anticholinesterase drugs were insignificant in all groups. 3) Both T1 and the ratio of the 4th twitch height to T1 (T4 ratio) were recovered above 75% of control within 30 minutes after injection of each anticholinesterase drugs in all groups, but there was significant slow progressing in edrophonium group. Comparing with same height of T1 the T4 ratio was not greater in edrophonium than in neostigmine or pyridostigmine. 4) The simultaneous administration of anticholinesterase drug and atropine (0.02 mg/kg) resulted the minimal changes in mean arterial pressure (+/-7% compared with prior to injection) or heart rate (+/-10% compared with prior to injection) from 5 minutes to 60 minutes after injection in all groups. In conclusion, although it was not thought that enzyme inhibition may be the sole factor, it should be considered to use succinylcholine or ester type of local anesthetics in patients who had recently received anticholinesterase drugs for reversal of nondepolarizing neuromuscular blockade, or for treatment of myasthenia gravis and glaucoma.

Comparison of Edrophonium and Neostigmine for reversal of the effects of Vecuronium / 대한마취과학회지

Until recently edrophonium has not been used in clinical anesthesis because of its short duration of action and poor anticholinesterase activity. However there has been a renewed interest in the use of edrophonium for the reversal of the new intermediate acting relaxants, vecuronium and atracurium, which have a fast spontaneous recovery rate. Edrophonim in sufficient dosages may produce a fast onset of antagonism of non-depolarizing neuromuscular blockade with minimal muscarinic side effects. The porpose of this study was therefore to compare the efficiency of edrophonium and neostigmine in reversal of a profound neuromuscular blockad following continuous infusion of vecuronium (0.06 mg/kg/hr). Recovery of T1 and T4 twitch height, change of heart rate and mean arterial pressure were obsered after antagonism with control mixture group (n=10): neostigmine 0.04mg/kg and atropin 0.02 mg/kg, and experimental mixture group (n=9): edrophoninm 0.5mg/kg and atropine 0.007 mg/kg were evaluated respectively at the 10% spontaneous recovery of T1 twitch height. Recovery of T1 was more faster in the edrophonium group than in the neostigmine group but it was significant until 5 minutes after antagonism (p<0.05) and recovery of T4 was also significantly faster in the edrophonium group until 5 minutes after antagonism but thereafter, conversly faster in the neostigmine group than in the edrophonium(p<0.05). Changes of heart rate with +/-5% after edrophonium administration were observed. We conclude that edrophonium provides a more rapid antagonism within 5 minutes after antagonizing vecuronium infusion, and small change in heart rate, but no other any advantage in using edrophomine instead of neostigmine for reversal after 5 minutes.