Electrogastrography for suspected gastroparesis





Introduction


Electrogastrography refers to the noninvasive method for recording and analyzing gastric myoelectrical activity (GMA) from electrodes placed on the upper abdominal surface . Electrogastrography methods are used to record electrogastrograms (EGGs) which measure GMA. The normal frequency of GMA in humans is approximately 3 cycles per minute (cpm) . The EGG signal measures GMA which includes ongoing gastric slow waves and the plateau and action potentials that occur with circular muscle contractions . Thus, the EGG measures overall GMA: The sum of slow waves and electrical events related to contractions that are ongoing in the stomach during fasting and after ingestion of liquid or solid foods or other stimuli.


Gastric dysrhythmias, on the other hand, are abnormal electrical events termed tachygastria, bradygastria, and mixed dysrhythmias . Gastric dysrhythmias develop when interstitial cells of Cajal (ICCs) are depleted and 3 cpm GMA disappears. If severe ICC depletion occurs, then gastric dysrhythmias and gastroparesis develop . Lessor ICC depletion, gastric dysrhythmias, and normal gastric emptying are found in patients with functional dyspepsia/chronic unexplained nausea (CUNV) . The ICCs are the pacemaker cells, predominantly located in intramuscular areas of gastric circular muscle and in myenteric plexi between the circular and longitudinal muscle layers . Gastric dysrhythmias are also found in a variety of conditions in which nausea and upper gastrointestinal symptoms are prominent .


Gastroparesis is defined as delayed gastric emptying in the absence of mechanical obstruction . In patients with gastroparesis, EGG recordings may reveal normal 3 cpm GMA or dysrhythmic GMA in response to the water load satiety test (WLST) . In patients with postprandial distress symptoms or gastroparesis-like symptoms, either normal 3 cpm GMA or dysrhythmic GMA is elicited by the WLST . Normal 3 cpm was found in t 16% of patients with diabetic gastroparesis and in 40% of patients with functional dyspepsia—postprandial distress . The diagnosis of normal or dysrhythmic GMA is important in understanding the pathophysiology of gastroparesis and in establishing subtypes of gastroparesis which can affect treatment approaches. In the sections below, the physiological basis and clinical use of electrogastrography in the diagnosis of normal or dysrhythmic GMA in patients with suspected gastroparesis are reviewed.


Electrogstrography and gastric myoelectrical activity of the stomach


Normal 3 cpm gastric slow waves: Pacemaker cells of the stomach


The stomach is a complex neuromuscular organ ( Fig. 15.1 ). Contractions and relaxations of the gastric fundus, corpus, antrum, and pylorus are neuromuscular events under myoelectrical, neurological, and hormonal control . Gastric peristaltic contractions are coordinated by the pacesetter potential or slow wave activity of the stomach. The term gastric slow waves will be used in this chapter. Gastric slow waves originate in the pacemaker region on the greater curvature of the stomach, between the fundus and the corpus ( Fig. 15.1 ). Slow waves are electrical depolarization and repolarizations travel circumferentially and migrate distally with increasing velocity and amplitude at a rate of approximately 3 cpm in humans . The slow waves control the frequency and propagation of velocity of the normal 3 per minute gastric peristaltic contractions. The fundus of the stomach has little or no intrinsic slow wave activity.




Figure 15.1


Diagram of major anatomical regions of the stomach (top) and detail of the relationships among circular muscle, longitudinal muscle, interstitial cells of Cajal (myenteric and intermuscular), and myenteric neurons in the gastric wall. The interstitial cells of Cajal (ICCs) located in the myenteric plexus area and the circular muscle layer are the pacemaker cells of the stomach that produce the 3 cpm slow waves. Slow waves are linked to plateau and spike potentials which are electrical events that occur during circular muscle contractions that migrate distally to form gastric peristaltic waves.


Gastric slow waves are generated by the ICCs. The ICC networks within the circular muscle control the frequency of depolarization of the circular smooth muscle cells . In the normal stomach with normal numbers of ICCs, the slow wave frequency ranges from 2.5 to 3.7 cpm or approximately 3 cpm . The density of ICCs is greater in the distal antrum than the corpus. GMA amplitude and velocity are greatest in the terminal 3–4 cm of the antrum . The ICCs also form synapses with the enteric neurons of the intrinsic nervous system of the stomach. Inputs from the enteric nervous system and the parasympathetic and sympathetic nervous systems to the stomach are transmitted to the ICCs and affect the slow waves and thus modulate contraction and relaxation of the circular muscle cells through these relationships that inhibit or promote gastric peristaltic contractions .


Gastric action potentials, plateau potentials, and circular muscle contractions


Circular muscle contractions of the stomach wall occur during action potential or plateau potential activity . Action potential activity and plateau potential activities are linked to the slow waves that bring the circular smooth muscle membrane to the threshold of depolarization and contraction. Thus, normal 3 per minute gastric peristaltic waves are composed of electrical components—the 3 cpm slow waves linked with the action potential or plateau potential activity ( Fig. 15.2 ). These two electrical components produce the GMA recorded in the EGG. Consequently, the increase in amplitude of the GMA waves (20-second duration) after meals reflects the slow wave linked with plateau/action potentials that occurs every 20 s during the postprandial 3 per minute gastric peristaltic contractions ( Fig. 15.2 ) . The GMA recorded noninvasively with EGG in waves of 20-second duration methods accurately reflects GMA recorded simultaneously with serosal electrodes .




Figure 15.2


Gastric slow waves linked to plateau/action potentials propagate rapidly circumferentially around the stomach from the pacemaker region in the proximal stomach (shown as the thin ring) and migrate distally at increasing velocity and amplitude toward the pylorus (thick ring) every 20 s for a normal rate of 3 cpm. The normal 3 cpm GMA waves recorded from electrodes placed on the surface of the epigastrium (the EGG device) summate the ongoing gastric myoelectrical activity (GMA) as shown in the EGG tracing. The EGG recording measures myoelectrical waves of 20-second duration that summate propagation and amplitude of the wave front as it moves distally across the corpus and antrum. As a myoelectrical wave crescendos at the pylorus with faster velocity and higher amplitude, the next wave has begun to migrate distally from the pacemaker area. Thus, each wave in the normal EGG signal measures each wave of GMA that propagates across the corpus-antrum every 20 s.


Thus, slow waves and plateau/spike potentials generate changes in cellular myoelectrical activity, all of which are summed in GMA and measured in the EGG. During the fasted state, the GMA from the stomach reflects predominantly the gastric slow wave activity and additional myoelectrical activity from intermittent gastric contractions. Thus, the EGG activity during fasting may be relatively unstable. In contrast, after a homogenous meal such as water, barium, or soup, the 3 per minute gastric peristaltic contractions empty these stomach contents; and, the corresponding GMA shows increased amplitude and regularity of 3 cpm waves as recorded in the EGG from healthy subjects . Studies using dozens of electrodes positioned on the corpus-antrum show that the slow waves propagate circumferentially and distally to form an elegant electrical ring that originates in the proximal corpus, migrates to the proximal antrum, and accelerates and gains amplitude in the terminal antrum, the 3–4 cm of the prepyloric antrum ( Fig. 15.2 ). Thus, the rhythmicity and amplitude of the EGG signal measures the integrity of the GMA and ICCs in the mid and distal antrum.


Gastric dysrhythmias


Gastric dysrhythmias are abnormal frequencies that include bradygastrias (1–2.5 cpm), tachygastrias (3.7–10 cpm), and mixed gastric dysrhythmias (combinations of tachygastrias and bradygastrias) . These dysrhythmias are recorded using electrogastrography methods ( Fig. 15.3 ) . In patients with chronic nausea conditions, gastric dysrhythmias represent a pathophysiological abnormality related to several known mechanisms. First, gastric dysrhythmias are related to depletion of the ICCs. ICCs are severely depleted (0–2 ICCs per high power field) in patients with gastric dysrhythmias and gastroparesis . In contrast, subjects with normal 3 cpm GMA have 5 or more ICCs per high power field . Interestingly, less severe ICC depletion (3–4 ICCs per high power field) has been reported in patients with unexplained nausea, gastric dysrhythmias, and normal gastric emptying . Thus, gastric dysrhythmias are present in both gastroparesis and in patients with gastroparesis-like symptoms (functional dyspepsia, chronic unexplained nausea) and appear to be a biomarker for nausea .




Figure 15.3


EGG rhythm strips of GMA showing examples of gastric myoelectrical activity. (A) Normal 3 cpm GMA. Dots indicate peak amplitude of the EGG wave that measures the migrating 3 cpm GMA. (B) Tachygastria. Dots indicate peaks of the 6 cpm unifocal tachygastria. (C) Bradygastria with low amplitude. (D) Bradygastria with high amplitude.


Second, chronic mesenteric ischemia is associated with nausea and vomiting and gastroparesis with gastric dysrhythmias . Gastric dysrhythmias resolved when stents or grafts were placed in the arteries and normal blood flow and oxygenation to the stomach was restored. Thus, chronic hypoxemia and oxidative stress may be a mechanism affecting GMA. Gastric dysrhythmias were eradicated and 3 cpm GMA was restored after treatment and indicate that depletion of ICCs may not be the only mechanism for developing gastric dysrhythmias.


Third, drugs such as domperidone and cisapride that have actions on enteric neurons eradicate gastric dysrhythmias in some patient groups, indicating that enteric neural dysfunction is another potential mechanism underlying gastric dysrhythmias in some patients . In full-thickness biopsies of the stomach from patients with gastroparesis, the smooth muscle cells appear to be intact, but enteric neurons have deformed cell processes and ICCs are depleted to various extents as described above . Thus, gastric dysrhythmias appear to be due to several pathophysiological pathways that include but are not limited to Cajalopathy, enteric neuropathy, autonomic nervous system dysfunction, or combinations of all. Fig. 15.3 shows examples of normal 3 cpm GMA and bradygastria and tachygastria.


Electrogastrography in patients with suspected gastroparesis


Clinical electrogastrography is indicated in the comprehensive evaluation of patients with symptoms suggesting upper GI motility disorders such as unexplained early satiety, nausea and vomiting, bloating, and abdominal discomfort. Symptoms are unexplained because gallbladder and pancreas imaging studies, upper endoscopy, and routine laboratory tests are normal in these patients. Thus, standard structural disorders are excluded and gastric neuromuscular disorders should be considered.


Gastric emptying scintigraphy and electrogastrography are noninvasive diagnostic tests that define objective gastric neuromuscular disorders. Solid-phase gastric emptying tests using scintigraphy or wireless motility capsule may indicate normal, rapid, or delayed gastric emptying of test meals . The EGG test provides further diagnostic precision for these patients by determining the presence or absence of normal 3 cpm GMA (the presence of normal numbers of ICCs) in response to the WLST.


Recording high quality EGGs


EGGs are recorded by placing fresh EKG-type electrodes in standard positions on the surface of the epigastrium. The skin should be prepared by gentle abrasion before placement of the electrodes to reduce impedance. The amplitude of the EGG signal ranges from 100 to 500 µV and the signal must be properly amplified and filtered. A 0.016 Hz high-pass filter and a 0.25 Hz low-pass filter are used. These filters create a window from approximately 1 to 15 cpm through which myoelectrical signals pass during the EGG recording . The normal EGG rhythm is approximately 3 cpm (2.5–3.7 cpm) . Bradygastrias range from 1.0 to 2.5 cpm and tachygastrias from 3.7 to 10.0 cpm. The duodenal pacesetter potential frequency is approximately 10–12 cpm. Occasionally, the respiration rate is less than 15 breaths per minute, may be seen in the EGG signal, and may be confused with tachygastria or duodenal slow wave frequencies .


The recording of high quality, artifact-free EGG signals is essential to facilitate visual analysis and ensure accurate computer analysis of the signal . To avoid movement artifact and to obtain high quality EGG recordings, the test must be performed in a quiet, warm room with the subject seated in a comfortable recliner with the back tilted to 30–45 degrees. The main source of artifact in the EGG signal is created by the subjects coughing, talking, or creating body movements during the recording. The EGG signal is reviewed visually for frequencies in the signal and for movement artifact that disrupts the EGG signal. These minutes of movement-induced artifact must be marked by the assistant who is always monitoring both the patient and the recording so that the artifact events are not used for computer analysis. The digitized EGG signals are subjected to fast Fourier transform to extract the frequency information present in the signal. The frequency data are presented as running spectral analyzes. Computer analysis allows for quantitative expression of the EGG signal as described below.


Provocative test meals and EGG recordings


Non-caloric WLST


The provocative WLST is used to assess the GMA response and symptoms elicited by the ingestion of the water load. The GMA evoked by the WLST is compared to results from healthy subjects . Provocative tests using water loading also reflects the capacity or accommodation of the stomach without the confounding neuroendocrine effects elicited by a caloric meal.


The standard clinical EGG test includes a baseline recording for approximately 15 minutes, followed by WLST. The test is performed with the patient having faster after midnight and prokinetic drugs and narcotics stopped for 7 days before the test. During the WLST the subject drinks cool water until they are “completely full” within a 5-minute time limit. Healthy subjects ingested an average of 557 mL in the 5-minute time period; 95% of healthy subjects consumed 238 mL or more in the 5-minute time limit . In another study all healthy subjects ingested more than 300 mL of water in the 5-minute time limit . In the NIH-sponsored Gastroparesis Clinical Research Consortium, 24% of patients with diabetic gastroparesis consumed less than 238 mL of water during the WLST . Ingestion of abnormally low WLST volumes suggests poor gastric accommodation is associated with increased symptoms and decreased gastric emptying . In patients with idiopathic and diabetic gastroparesis, lower volumes of water ingested during the WLST were associated with greater fullness and poorer gastric emptying . Other test meals can be studied.


Caloric meals


The caloric meal test (CMT) using Ensure® (consumed as 150 mL volumes every 4 minutes until the subject is satiated) has been used as a test meal for symptoms and gastric accommodation . During the CMT patients with diabetic gastroparesis consumed 427 mL±287 mL over an average of 8 minutes . Nausea, bloating and abdominal discomfort increased after the CMT in these patients and the increase in intensity of symptoms was greater than after the WLST . The 3 cpm GMA response after the CMT was greater compared with the WLST before but not after 24 weeks of intensive insulin therapy .


Tests of gastric motility to determine if gastroparesis is present have used caloric meals, usually solid meals like the Eggbeaters sandwich, to stimulate the stomach contractions and determine residual food at 2 and 4 hrs. after ingestion of the meal . In contrast liquid emptying begins almost immediately after ingestion and follows a generally exponential curve . Small amounts of liquid nutrients enter the duodenum and stimulate duodenal receptors and neuroendocrine responses that may also affect postprandial GMA and symptoms. Thus, for nutrient test meals there is gastric accommodation, trituration and emptying factors and duodenal receptor-neuroendocrine responses to the specific meal that may also affect stomach GMA and symptoms. As described above the CMT induced more symptoms than the WLST in patients with diabetic gastroparesis, a difference that may be due to neurohormonal responses to the calories and subsequent effects on symptoms and GMA . The GMA responses to the Ensure caloric meals in healthy control subjects have not been established. Different test meals, from solids to liquids to no calories to various calorie content, will stimulate different GMA responses


Analysis of the EGG signal


Visual analysis


Proper analysis of the EGG signal requires visual inspection of a high-quality EGG signal. The EGG recording is inspected for the presence of normal 3 cpm activity, tachygastrias, or bradygastrias. It is extremely important to identify artifacts in the EGG signal which may be created by movement of the limbs, deep breathing, coughing, or talking during the recording .


Computer analysis


Computer analysis determines the frequency and power (amplitude) components in the EGG signal. The frequency component is the most reliable and interpretable of the clinical EGG parameters that can be quantified in clinical electrogastrography. The human GMA averages approximately 3 cpm and 2 standard deviations of the mean defines the normal GMA frequency range of 2.5–3.7 cpm . This normal range was established with studies using serosal electrodes and confirmed with simultaneous EGG recordings. In studies using dozens of electrodes placed on the corpus-antrum in anesthetized subjects undergoing abdominal operations, the normal range was confirmed . Table 15.1 shows the frequencies of GMA relevant to human studies. The normal range in humans is as follows: normal, ≥2.5–≤3.7; bradygastrias, <2.4 cpm; and tachygastrias, >3.7 cpm–<10 cpm . The duodenal slow wave frequency is 10–13 cpm and respiratory movements can also occur in the 10–15 cpm range.



Table 15.1

Gastric myoelectrical activity (GMA) frequency ranges.



















GMA categories GMA frequency ranges
Bradygastria 1.0–2.5 cpm
Normal 2.5–3.7 cpm (referred to as 3 cpm)
Tachygastria 3.7–10.0 cpm
Duodenal-respiratory 10.0–15.0 cpm


Computer analyzes of GMA in response to caloric test meals also has been studied. Chen et al used 250–400 Cal solid meals with less than 35% fat to stimulate the stomach and record GMA . The computer analysis pioneered by Chen et al derives the dominant normal GMA frequency defined as 2–4 cpm with bradygastrias <2 cpm and tachygastrias >4 and <9 cpm . The power ratio reflects the GMA before and after the test meal and a ratio >1 reflects increased post-prandial contractility . Other computer calculated parameters include the percentage of time that the dominant frequency resides within the normal range (70% of the time or more) and in the dysrhythmic ranges (30% of the time or more) .


Clinical electrogastrography and diagnoses


Normal 3 cpm GMA in Response to the WLST in Healthy Subjects Fig. 15.4 shows a normal 3 cpm GMA response to a normal WLST volume. The EGG signal in the rhythm strip shows clear 3 cpm GMA. The spectral analysis also shows the clear peaks in the 3 cpm range, especially after the water load. This is a normal test of GMA rhythm and gastric capacity, suggesting normal numbers of gastric ICCs and normal gastric capacity or accommodation. The percentage distribution analysis takes into account all the myoelectrical activity in the four relevant frequency ranges and patient results are compared with healthy controls as shown in Fig. 15.5 . The percentage distribution of EGG power in the 3 cpm range is normal at baseline and 10 and 30 minutes and above normal at 20 minutes after the WLST . The running spectral analysis of the EGG signal shows consistent peaks in the 3 cpm range. Table 15.2 shows the normal ranges for the percentages of interest in the four frequency ranges before and after the WLST . The data in the EGG signal may also be expressed as the power ratio, the postprandial to preprandial ratio of the percentage distribution calculation in the four frequency ranges, and the percentage of time in the dominant frequency .


Feb 4, 2021 | Posted by in GASTROENTEROLOGY | Comments Off on Electrogastrography for suspected gastroparesis
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