Symptomatic improvement of diffuse esophageal spasm after botulinum toxin injection

Diffuse esophageal spasm, an uncommon esophageal motility disorder, has recently been defined using high-resolution manometry. Patients with distal esophageal spasm usually complain of chest pain or dysphagia. The etiology and pathophysiology of this disorder are poorly known, and treatment options are limited. However, some options to improve symptoms are available, including endoscopic injection of botulinum toxin. Nevertheless, few reports have described the effects of endoscopic injection of botulinum toxin in patients with symptomatic diffuse esophageal spasm with clear endoscopic and high-resolution manometry images. Here, we report a case of diffuse esophageal spasm diagnosed with high-resolution manometry and treated by endoscopic injection of botulinum toxin with good results at the 7-month follow-up.     

Transition from peristaltic esophageal contractions to diffuse esophageal spasm

A patient with dysphagia and chest pain was shown by manometry to have high-amplitude peristaltic esophageal contractions (nutcracker esophagus). Worsening symptoms over the next two years led to the performance of repeated manometric studies, which showed diffuse esophageal spasm. This demonstration of a transition from nutcracker esophagus to diffuse esophageal spasm lends further support for consideration of the nutcracker esophagus as a manometric disorder associated with chest pain or dysphagia. Furthermore, it suggests a pathophysiologic relationship between the nutcracker esophagus, a disorder with preserved peristalsis, and diffuse esophageal spasm, the classic dysmotility considered to be of neurogenic origin.     

The Treatment of Bronchial Asthma by Means of Hypnosis: As viewed by the allergist

The physician who wishes to treat by hypnosis, asthma or any other disorder in which spasm is a characteristic sign, symptom or symbol, must, in general, be familiar with the two chief types of reflexes. The therapist must also possess a detailed knowledge of the structure of the normal functions of the organ which is the site of the spasm, and must know how these functions may be changed by the disorder when it is the result of conditioned reflexes and how they may be returned to normal by deconditioning the patient.     

Familial dysphagia

The etiology of achalasia and diffuse esophageal spasm remains unknown. We report on two families (father/son, mother/son) with achalasia and esophageal spasm, respectively, who were examined by radiology, endoscopy and manometry. One patient (mother) died from aspiration pneumonia. These observations support the hypothesis of a genetic trait in some cases of esophageal motility disorders. In addition, the coincidence of familial achalasia and esophageal spasm is in support of a close relationship of both diseases. Achalasia is a potentially letal disorder.     

Botulinum toxin in the treatment of diffuse esophageal spasm

Diffuse esophageal spasm is a primary esophageal motility disorder. The prevalence is 3–10% in patients with dysphagia and treatment options are limited. This review summarizes the treatment of diffuse esophageal spasm, including pharmacotherapy, endoscopic treatment, and surgical treatment with a special focus on botulinum toxin injection. A PubMed search was performed to identify the literature using the search items diffuse esophageal spasm and treatment. Pharmacotherapy with smooth muscle relaxants, proton pump inhibitors, and antidepressants was suggested from small case series and uncontrolled clinical trials. Endoscopic injection of botulinum toxin is a well‐studied treatment option and results in good symptomatic benefit in patients with diffuse esophageal spasm. Surgical treatment was reported in patients with very severe symptoms refractory to pharmacologic treatment. This article summarizes the present knowledge on the treatment of diffuse esophageal spasm with a special emphasis on botulinum toxin injection. Endoscopic injection of botulinum toxin is presently the best studied treatment option but many questions remain unanswered.     

Prognostic Links Between OCT-Delineated Coronary Morphologies and Coronary Functional Abnormalities in Patients With INOCA

ObjectivesWhether there are prognostic links between coronary morphologies and coronary functional abnormalities was examined in ischemia and nonobstructive coronary artery disease (INOCA) patients.BackgroundAlthough INOCA has attracted much attention, little is known about the prognostic impact of coronary morphologies in this disorder.MethodsA total of 329 consecutive INOCA patients were enrolled and underwent spasm provocation testing combined with lactate sampling for diagnosis of epicardial and microvascular spasm (MVS). On the basis of the functional tests, the patients were classified into 4 groups: a control group without epicardial spasm or MVS (n = 32), MVS alone (n = 51), diffuse spasm in ≥2 coronary segments (n = 204), and focal spasm in 1 segment (n = 42). In this population, optical coherence tomography imaging of the left anterior descending coronary artery was performed for evaluation of adventitial vasa vasorum (AVV) and intraplaque neovessels (IPN). Index of microcirculatory resistance was also measured.ResultsMVS frequently coexisted with diffuse (70%) and focal spasm (68%) with a good correlation between AVV and index of microcirculatory resistance (R = 0.353; p = 0.022). For a median follow-up of 1,043 days, focal spasm showed the worst prognosis (log rank p = 0.005), for which IPN was a significant prognostic factor. By contrast, diffuse spasm showed the greatest AVV with an intermediate prognosis. The prognostic value of INOCA was significantly enhanced by adding AVV and IPN to the physiological indices (area under the curve = 0.88 vs. 0.76; p = 0.048).ConclusionsThese results provide the first evidence that there are important prognostic links between coronary morphologies (evaluated by optical coherence tomography) and coronary functional abnormalities in patients with INOCA, indicating the importance of both evaluations in this population.     

Spectrum of coronary arterial spasm. Clinical, angiographic and myocardial metabolic experience in 29 cases

A relationship of coronary arterial spasm to variant angina pectoris, subendocardial ischemia, major ventricular arrhythmias and myocardial infarction has been demonstrated. In 29 patients, spasm was angiographically observed in normal-appearing coronary arteries (7 patients) as well as superimposed on various degrees of coronary atherosclerotic obstruction (22 patients). All patients experienced an atypical anginal syndrome; 16 patients also experienced typical exertional angina. Coronary spasm appeared to be a major contributory factor in eight occurrences of myocardial infarction and in 11 incidents of ventricular tachycardia, ventricular fibrillation and heart block.

Coronary spasm in the 29 cases was distributed in the following fashion: left main trunk, 6 cases; right main trunk, 12 cases; proximal left anterior descending artery, 13 cases; proximal circumflex artery, 1 case; distal left anterior descending artery, 1 case; and distal circumflex artery, 2 cases. In 5 cases coronary spasm was noted at multiple sites.

In contrast to findings in patients manifesting only typical exertional angina, the hemodynamic findings during spasm were those of a hypodynamic state. Left ventricular systolic pressure decreased from 138.9 ± 6.0 (mean ± standard error of the mean) to 113.2 ± 6.2 mm Hg; left ventricular end-diastolic pressure did not change significantly. Myocardial lactate extraction during spasm was invariably markedly reduced: −53.19 percent ± 15.44 (P < 0.001). However, the effect of coronary sinus pacing on myocardial lactate extraction was not significantly abnormal: +15.74 percent ± 6.66.

The respective roles of medical and surgical intervention are uncertain. Only 3 patients had a completely satisfactory pharmacologic response to nitrates alone or in combination with propranolol, and the condition of 5 others was partially improved; the remaining 21 patients were judged intractable to medical management. Coronary bypass surgery was performed as the ultimate recourse in 18 patients. However, short-term results reveal that only nine (50 percent) showed improvement, four (22 percent) had myocardial infarction during or after surgery and four (22 percent) died.

These studies confirm that coronary arterial spasm is a definite pathogenetic factor in a variety of acute myocardial ischemic syndromes. The incidence and full clinical significance of this functional disorder remain to be determined.     

Acetylcholine Rechallenge: A First Step Toward Tailored Treatment in Patients With Coronary Artery Spasm

ObjectivesThe present study aimed to assess the feasibility and clinical value of acetylcholine (ACh) rechallenge for the detection of coexisting epicardial and microvascular spasm and to determine the efficacy of nitroglycerin in these spasm endotypes.BackgroundThe coexistence of epicardial and microvascular spasm is difficult to identify; thus, its frequency is unknown. Nitroglycerin treatment is equally recommended for both epicardial and microvascular coronary spasm despite contradictory data.MethodsIn this multicenter study, 95 patients with coronary spasm were included to undergo ACh rechallenge, which consisted of repeated ACh provocation 3 minutes after intracoronary nitroglycerin administration using the same dose that previously induced spasm.ResultsIn total, 95 patients (age 61 ± 12 years, 69% female) were included. Fifty-five patients (58%) had microvascular spasm, and 40 patients (42%) had epicardial spasm during initial ACh provocation. In 48% of patients with epicardial spasm, ACh rechallenge revealed coexisting nitroglycerin-persistent microvascular spasm. Nitroglycerin administration before ACh rechallenge prevented reinducibility of epicardial spasm in all patients with focal spasm and in 80% of patients with diffuse spasm. Microvascular spasm was prevented in only 20% by prior nitroglycerin administration but was attenuated in another 49% of patients.ConclusionsThis study demonstrates a high frequency of epicardial spasm with coexisting nitroglycerin-persistent microvascular spasm. Intracoronary nitroglycerin was very effective in preventing reinducibility of epicardial spasm, whereas it prevented microvascular spasm in only 20% of patients. ACh rechallenge is a novel method that facilitates the detection of coexisting spasm endotypes and may pave the way towards tailored treatment of vasospastic angina.     

Transition from diffuse esophageal spasm to achalasia.

A 19-year-old man first presented with clinical, radiological, and manometric features of diffuse spasm. Within a year his motility disorder progressed to "vigorous" and, finally, classic achalasia. After pneumatic dilatation and subsequent long myotomy, the features of classic achalasia disappeared and he again exhibited radiological and manometric evidence of "vigorous" achalasia. The evolution of this patient's disease provides evidence that diffuse spasm and achalasia are different stages of the same disease and lie at opposite ends of a spectrum of related esophageal motility disorders.     

Sororal occurrence of diffuse esophageal spasm

Summary In this report, we have described two sisters with classical symptoms, radiological appearances, and manometric features of diffuse esophageal spasm. To the best of our knowledge, familial occurrence of this disorder has not been documented previously.     

Raynaud's disease: A review of its mechanism,with evidence that it is primarily a vascular disease

After digesting some of the literature and studying three cases of Raynaud's disease, we feel that the evidence is greatly in favor of the conclusion that the disease is primarily a vascular, and not a sympathetic, disorder. Sympathectomy is beneficial objectively because it eliminates the vasomotor influence which is normal in any given case. It is beneficial subjectively because it abolishes the aching and stinging pain of vasoconstriction. (Whether the relief of this type of pain is brought about by cutting afferent sympathetic fibers or by an alteration in the threshold for pain following the interruption of efferent sympathetics remains unsolved.) Our contention is based largely on the following major considerations: (1) As Lewis has shown, the vascular spasm caused by cold water and its release in warm water are strictly local phenomena. (2) We have demonstrated that, after preganglionic or postganglionic sympathectomy, the hands still retain the local disorder objectively, that is, cold continues to cause the color changes. This objective response is diminished in mild cases, but only to a degree that would be expected after eliminating the normal sympathetic vasomotor influence. (3) When a patient is taken nude into a refrigerator, and kept there long enough to cause a fall in central temperature, and, at the same time, one of his hands is kept at room temperature, the latter does not show evidence of vascular spasm, either subjectively or objectively, even though the exposed hand reacts severely. One is justified in assuming that, if the sympathetic system is responsible for the vascular spasm, the hand at room temperature under these circumstances should react somewhat like the other hand.     

非典型性冠状动脉痉挛患者的临床特点及近期预后

目的总结非典型性冠状动脉痉挛患者的临床特点。方法选择临床具有静息性胸痛或胸闷,且冠状动脉造影无显著狭窄的64例患者进行乙酰胆碱冠状动脉痉挛激发试验,将乙酰胆碱试验阳性即冠状动脉痉挛患者根据胸痛或胸闷发作时心电图上是否有ST段抬高分为典型变异型心绞痛组（典型组）和非典型变异型心绞痛性冠状动脉痉挛组（非典型组）,比较两组的临床症状特点（危险因素、心电图和核素心肌灌注显像负荷试验结果以及冠状动脉造影和乙酰胆碱试验的影像学）。结果共有46例（72％,46／64）患者诱发冠状动脉痉挛,其中典型组和非典型组分别为12及34例。典型组的平均年龄偏低（P〈0．05）,血脂代谢紊乱在非典型组更常见,运动心电图试验两组多为阴性,核素灌注心肌显像负荷试验两组均表现有反向再分布,冠状动脉造影典型组多为轻度局限性狭窄或节段性内膜不光滑,肌桥发生率更高,乙酰胆碱试验多诱发节段性痉挛。而非典型组为弥漫性血管细小、内膜不光滑、僵硬,血管迂曲伴远端血流缓慢,乙酰胆碱试验多诱发弥漫性血管痉挛,并可见多支血管同时痉挛。结论非典型性冠状动脉痉挛较典型变异型心绞痛更常见,且具有一定的特征性,应引起临床医生高度重视。     

Methacholine provocation of prinzmetal's variant angina pectoris: A revised perspective

We report 13 patients with unequivocal Prinzmetal's variant angina pectoris as the entire experience with this syndrome during a 7-year period in a single institution. The clinical diagnosis of this relatively uncommon disorder is emphasized. Five patients were given 10 mg of methacholine subcutaneously. Three demonstrated subsequent delayed appearance of chest pain, ECG change, and coronary vasospasm following early appearance of muscarinic effects. Two Prinzmetal patients had no provocation of variant angina following methacholine, though they did experience significantly less blood pressure fall in response to muscarinic provocation. Another 23 subjects with incompletely explained chest pain given methacholine had neither ECG change nor spasm. Methacholine provocation of variant angina need not necessarily implicate a parasympathomimetic mechanism for otherwise spontaneous episodes. Rather, provocation would appear to occur via the customary reflex adrenergic response to drug-induced hypotension. Methacholine is probably safe though unreliable as an agent to be used for spasm provocation.     

Treatment of symptomatic diffuse esophageal spasm by endoscopic injections of botulinum toxin: a prospective study with long-term follow-up.

BACKGROUND: Diffuse esophageal spasm is a rare esophageal motility disorder for which there are no satisfactory pharmacologic alternatives for treatment. The aim of this study was to investigate whether botulinum toxin (BTX) injection is an effective short- and long-term treatment for patients with symptoms caused by diffuse esophageal spasm. Whether recurrence of clinical symptoms can be successfully retreated by BTX injection was also studied. METHODS: Nine symptomatic patients (6 women, 3 men; 57-86 years) with manometrically proven diffuse esophageal spasm underwent BTX injection. One hundred IU BTX were diluted in l0 mL of saline solution and injected endoscopically at multiple sites along the esophageal wall beginning in the region of the lower esophageal sphincter and moving proximally in 1- to 1.5-cm intervals, and into endoscopically visible contraction rings. Symptom scores based on an analogue scale for dysphagia, regurgitation, and noncardiac chest pain were assessed before and after therapy, 1 day thereafter, and at 1 and 6 months. RESULTS: Symptoms improved immediately in 7 (78%) patients after 1 injection session. After 4 weeks 8 (89%) patients were in remission with a decrease in total symptom score. The total symptom score decreased from a median 8.0 (interquartile range: 6.75; 9.0) before treatment to 2.0 (1.5; 3.75) after 1 day (p < 0.01) and to 2.0 (interquartile range: 0.75; 3.0) after 1 month (p < 0.01). After 6 months all 8 patients with a response at 1 month still had a symptom score of 3 or less without further treatment. Subsequently 4 patients required reinjection 8, 12, 15, or 24 months after the initial treatment with similarly good results. No serious adverse effects were observed. CONCLUSIONS: BTX injection at several levels of the tubular esophagus is an effective treatment for patients with symptoms caused by diffuse esophageal spasm. Symptom relapse can be effectively treated by repeated BTX injection.     

Control of hypereosinophilic syndrome-associated recalcitrant coronary artery spasm by combined treatment with prednisone, imatinib mesylate and hydroxyurea

Uncontrolled hypereosinophilic syndrome is frequently associated with cardiovascular consequences that cause significant morbidity and mortality. The present article reports on a patient with hypereosinophilic syndrome in whom recurrent, recalcitrant coronary artery spasm and associated cardiac arrest were the predominant cardiac manifestations. No valvular abnormalities, evidence of mural thrombi or other cardiac findings commonly associated with hypereosinophilic syndrome were detected, and cardiac function remained normal. The serum tryptase level was normal, cysteine-rich hydrophobic domain 2 (CHIC2) deletion analysis of bone marrow cells was negative and no evidence of mastocytosis or other hematological disorder was found in the bone marrow. To allow for the reduction of prednisone, interferon-alpha-2b was added to the patient's program, but caused aggravation of chest pain and was discontinued. However, a combination of reduced prednisone dosage, imatinib mesylate and hydroxyurea successfully controlled the eosinophilia, and thereafter, episodes of coronary artery spasm did not recur. The clinical features of the present case suggest that, in some patients, hypereosinophilia may manifest as resistant coronary artery spasm and that aggressive control of eosinophilia is necessary.     

Prognostic significance of the pattern of multivessel spasm in patients with variant angina.

Multivessel spasm in variant angina is believed to be a major prognostic factor. Three patterns of multivessel spasm have been detected: (1) spasm at different sites on different occasions (migratory spasm); (2) spasm sequentially affecting 2 different sites (sequential spasm); and (3) simultaneous spasm at more than 1 site (simultaneous spasm). The present study investigated the prognosis based on this factor for variant angina without fixed coronary stenosis and examined the influence of multivessel spasm on cardiac events. Twenty-six patients were diagnosed as having variant angina without fixed coronary stenosis using 12-lead 24-h ECG recording system and coronary cineangiography. These patients were followed up prospectively for 57.1+/-7.6 months. Of the 26 patients 13 had single-vessel spasm, 6 had migratory multivessel spasm angina, and 7 showed sequential and/or simultaneous multivessel spasm angina. The survival free of serious cardiac events and of all cardiac events was significantly lower for patients with sequential and/or simultaneous multivessel spasm than for those with migratory multivessel spasm (p<0.05, p<0.05), whereas for patients with migratory multivessel spasm the difference comparison with single-vessel spasm did not attain statistical significance (p = ns, p = ns). The results of this study suggest that there seems to be a high-risk subgroup (i.e., sequential and/or simultaneous multivessel spasm) among patients with variant angina.     

Efficacy of aripiprazole in sulpiride-induced tardive oromandibular dystonia

Tardive dystonia is a side effect of dopamine receptor-blocking agents, which are mainly used as antipsychotic drugs. The treatment of tardive dystonia is difficult and often unsuccessful. An 82-year-old woman experienced mandibular deviation to the left due to spasm of the masticatory muscles with involuntary chewing movement and Parkinsonism. She had been treated with sulpiride for motility disorder for 5 years. Parkinsonism almost disappeared after the withdrawal of sulpiride, but tardive oromandibular dystonia showed no improvement. Aripiprazole treatment at 3 mg/day improved tardive oromandibular dystonia without worsening Parkinsonism. Low-dosage aripiprazole may be effective for tardive oromandibular dystonia in patients with no other psychiatric disorder.     

Deglutition syncope and atrioventricular block selectively induced by hot food and liquid

Deglutition syncope is an uncommon disorder in which loss of consciousness follows swallowing. At least 26 cases have been reported. The cause appears to be an esophagocardiac vagal reflex producing atrial bradyarrhythmias or atrioventricular (AV) block.¹ Most cases have been associated with esophageal disease.² In some cases with no esophageal disease, a history consistent with esophageal spasm may be present.³ We recently encountered a patient in whom swallowing only hot substances could induce lightheadedness or syncope due to transient complete AV block.     

Comparison of clinical and laboratory findings between patients with diffuse three-vessel coronary artery spasm and other types of coronary artery spasm

Our purpose was to compare patients with diffuse three-vessel coronary artery spasm and other types of coronary artery spasm without significant organic stenosis, and to elucidate clinical characteristics and risk factors. Patients were divided into two groups: group I consisted of 26 patients showing other types of coronary artery spasm; group II consisted of 5 patients with diffuse three-vessel coronary artery spasm. The mean age of patients in groups I and II was 52 and 50 years, respectively. The incidence of variant angina was higher in men than in women. The incidence of smoking was high in each group, but not significantly different. Exercise tests showed no significant differences between groups. All mean values of laboratory data, including lipoprotein (a) and low-density lipoprotein cholesterol in the two groups, were within normal ranges. There was no significant difference between groups. The incidence of spontaneous spam was much higher in patients with diffuse three-vessel coronary artery spasm (P < 0.01). Electrocardiographic (ECG) findings before the spasm were almost normal. All 5 patients with diffuse three-vessel coronary artery spasm demonstrated no important ST segment changes with episodes of angina during a coronary angiography on 12-lead ECG, compared to patients with other types of coronary artery spasm (P < 0.01). First, we conclude, diffuse three-vessel coronary artery spasm mostly occurs spontaneously. Second, we emphasize that diffuse three-vessel coronary artery spasm must be considered when 12-lead ECG shows no important ST segment changes with episodes of angina. Third, it is not easy to distinguish diffuse three-vessel coronary artery spasm from other types of coronary artery spasm on the basis of history, laboratory data, or electrocardiographic findings, including exercise tests. © 1996 Wiley-Liss, Inc.     

Ampulla of Vater/duodenal wall spasm diagnosed by antroduodenal manometry

Patients with chronic epigastric to right upper quadrant pain are often considered to have gallbladder or sphincter of Oddi dysfunction, but standard tests are nondiagnostic. In 62 consecutive patients with this complaint undergoing antroduodenal manometry, we correlated a change in duodenal motility with spasm of the ampulla of Vater/duodenal wall. This distinctive motility pattern occurred and was analyzed in 35% of patients. It is characterized by increased duodenal wall tone with phasic contractions of 19–22 or 41–44 contractions/min or by phasic activity alone. The subjects with spasm also underwent cholecystokinin cholescintigraphy, and 50% showed either significantly delayed gallbladder emptying or hilum to small intestine emptying, or both. The disorder appears to be secondary to a loss of neural inhibitory control and a dysfunctional small-bowel pacemaker. Antroduodenal manometry is an essential diagnostic procedure that complements sphincter of Oddi manometry in evaluation of unexplained right upper quadrant pain.