No Evidence of Impaired Gastric Emptying in Early Huntington‘s Disease

According to the PLOS Currents Huntington,

"No Evidence of Impaired Gastric Emptying in Early Huntington‘s Disease
November 16, 2011 · Epidemiology


Authors

Carsten Saft
Jürgen Andrich
Marc Fälker
Sarah Gauda
Sina Küchler
Dirk Woitalla
Oliver Goetze




Abstract

Background: Several factors, such as dysphagia, an increased motor activity, increased metabolic rate and a hypermetabolic state have been discussed as contributing to weight loss even at the early stages of Huntington’s Disease (HD). Aim of this pilot study was to investigate gastric emptying as a possible reason for weight loss in HD.

Methods: 11 HD participants at early stages of the disease and matched controls were investigated by using the well-established and non-invasive 13C-octanoate breath test. The “Gastroparesis Cardinal Symptom Index” and the “Short-Form Leeds Dyspepsia Questionnaire” were used for clinical evaluation of gastroparesis or dyspepsia.

Results: When compared to standard values ​​given in literature and controls all HD patients had normal breath test results. There was no evidence of gastroparesis or dyspepsia. There was a correlation of breath test results with the cognitive and functional performance of HD participants.

Conclusion: According to our data, there is no evidence of impaired gastric emptying in early HD. We can not exclude that gastric emptying contributes to weight loss at more advanced stages of the disease.

Corresponding author: PD Dr. med. Carsten Saft, Department of Neurology, Huntington-Center NRW, St. Josef Hospital, Gudrunstrasse 56, 44791 Bochum, Germany, E-mail: carsten.saft@ruhr-uni-bochum.de

§ Carsten Saft and Jürgen Andrich contributed equally to this work
Funding Statement
The study was supported by a FoRUM grant, University of Bochum (AZ: F506-2006). Oliver Götze was supported by the DFG (Gö 13582/1).
Introduction

Weight loss is a main feature in Huntington’s disease (HD) and was found to be manifest even at early stages of the disease. [1][2][3][4][5] Multifactorial causes, such as decreased caloric intake due to dysphagia and a higher energy expenditure due to increased motor activity have been discussed as being a possible reason for weight loss especially at the advanced stages of the disease. [6][7][8][9][10] Using a whole body indirect calorimetry in both early stage HD patients and the R6/2 transgenic mouse model of HD, Goodman and colleagues were able to demonstrate that patients with early HD tended to have a negative energy balance for reasons not related to their movement disorder, which was paralleled in the transgenic R6/2 mice. [4] This leads to the assumption of an increased metabolic rate as a main reason for weight loss in HD, which is supported by other experiments in the transgenic R6/2 mice. [4][11][12] In a study investigating the direct relation between the number of CAG repeats in the mutant huntingtin gene and weight loss, Aziz and colleagues found a correlation between both of these factors and discussed a hypermetabolic state as being a reason for weight loss, occurring even at early stages of the disease. [13] They discussed a hypermetabolic state as being likely to stem directly from interference of the mutant protein with cellular energy homeostasis and thus reflecting fundamental pathologic mechanisms underlying HD and not to be secondary to hyperactivity. Since mutant Huntingtin (mtHtt) is not only expressed in the brain of HD patients, but also in the gastrointestinal (GI) tract, a recently published study investigated the GI tract in the R6/2 mice model for HD. This study describes a loss of enteric neuropepitdes, a decreased mucosal thickness and villius length and also an impaired gut motility, diarrhea, and malabsorption of food, suggesting that GI dysfunction plays an important role in weight loss in HD mice. [14]

In addition, gastrointestinal dysfunction is discussed as being the main reason for weight loss in Parkinson’s disease (PD). [15] In a study using a solid meal and the 13 C-sodium octanoate breath test for measurement of gastric emptying in patients with PD, Goetze and colleagues found 88% of PD patients suufered from delayed gastric emptying when compared with controls. The severity of motor impairment was associated with gastroparesis. [16] Several other studies confirm an impaired gastric emptying in PD, some of them with a rate of 100% of PD patients. [16][17][18][19][20][21] One study describes a 60% delay in gastric half emptying time in the PD patient group after a solid test meal using the non-invasive 13 C-sodium octanoate breath test for evaluation of gastric emptying. [17] Neuropathological findings suggest enteric dysfunction to be one of the initial pathophysiological events in PD. [16][22] Central and enteric nervous system involvement in PD is discussed as being a pathophysiologic basis for this dysfunction. [15]

Autonomic nervous dysfunction was found to be present in HD, too. [23] Thus, the aim of the current study was to investigate gastric emptying in early HD patients without medication as a possible additional reason for weight loss by using the well-established 13 C-octanoate breath test. [16][17][18][19][20][21][24]
Methods





Participants

11 manifest HD patients with genetically confirmed diagnosis and without any medication in at clinically early stages of the disease (Shoulson stage I/II) and 11 controls were recruited from the HD centre Bochum, Germany. [25] Participants with known concurrent gastrointestinal diseases or previous operations of the gastro-intestinal tract were excluded, as well as patients with other severe diseases, diabetes mellitus, severe respiratory dysfunction, and malignancies. Also participants with concurrent liver diseases or excessive alcohol consumption (50 g/d of ethanol) were excluded. All participants had lab parameters for ALT, AST, LDH, cholesterol and triglycerides within the normal range, as well as normal findings for the ultrasonography of the upper abdomen. Pregnant and breast-feeding women were excluded. All HD participants underwent neurological investigation and were scored according to the UHDRS items “motor scale” (MS), “total functional capacity” (TFC) “independence scale” (IS) and the items verbal fluency test, symbol digit test, interference test, color naming and color reading which were summarized as “cognitive score” (CS). [26] Fine motor skills were additionally measured by simple (tapping; higher motor impairment leads to lower test results) and complex (pegboard; higher motor impairment leads to higher test results) instrumental movement tests. [27][28][29][30] The severity of depressive symptoms was assessed by using the Beck’s depression inventory (BDI) and Hamilton depression rating scale. [31][32] Clinical characteristics of all HD patients are given in table 1. In addition we calculated the disease burden score (DBS = [CAG repeat – 35.5] x age) for each subject. [33] The study was approved by the ethic committee of the Ruhr-University Bochum, Germany (registration-number 2719). Participants gave informed written consent according to GCP/ICH.

Parameter HD Participants Controls
Age [yr] 42.4 ± 8.4 (29-57) 48.9 ± 9.6 (38-69)
Gender (male/female) 3/8 3/8
BMI 22.5 ± 3.5 (16-30) 26.5 ± 6.4 (19-42)
Weight [kg] 63.6 ± 14.1 (42-85) 84.5 ± 22.5 (54-128)
Height [cm] 166.8 ± 10.1 (153-183) 178.2 ± 9.4 (164-190)
AO motor 39 ± 8.6 (25-51) –
AO psychiatric 38 ± 20.9 (29-50)a –
CAG expanded 45 ± 2.9 (42-51) –
Disease burden score 386.59 ± 66.06 (273-483) –
Disease duration [yr] 4.2 ± 2.5 (0.1-9) –

UHDRS MS 30.8 ± 18.7 (5-72) –
UHDRS TFC 10.2 ± 1.9 (7-12) –
UHDRS IS 81.8 ± 9.8 (70-100) –
UHDRS CS 195.1 ± 79.0 (98-346) –
Verbal fluency 22.5 ± 18.2 (4-69) –
SDMT 27.2 ± 10.6 (16-44) –
Stroop color 47.1 ± 17.1 (26-74) –
Stroop word 68.1 ± 22.8 (32-100) –
Stroop interference 29.5 ± 16.1 (10-59) –
Hamilton 12.8 ± 10.0 (1-26) –
Beck depression inventory 12.3 ± 13.4 (0-39) –

Tapping dominant 129.2 ± 44.8 (47-198) –
Tapping non dominant 99.4 ± 33 (38-161) –
Pegboard dominant [sec] 68.6 ± 24.8 (42.2-120.9) –
Pegboard non dominant [sec] 80.9 ± 40.2 (43.9-184.0) –

Table 1: Clinical characteristics of 11 HD patients and 11 matched controls; values are given as mean ± SD; range (min-max) in brackets; Abbreviations: BMI – body mass index, yr – years, AO – age at onset, a n = 6; UHDRS – unified Huntington´s disease rating scale, MS – motor score TFC – total functional capacity, IS – independence scale, CS – cognitive sum score, SDMT – symbol digit modalities test; sec – seconds. * – significant differences.






Test meal and 13C-octanoate breath test technique

The 13 C-octanoate breath test was used in the same way as described earlier. [16][17][18][34] In summary: After an overnight fasting each participant received a solid test meal consisting of an egg omelet of one egg, 60 g of white bread, 5 g of margarine and 150 ml of water (14 g of proteins, 26 g of carbohydrates and 9 g of fat, 241 kcal) labeled with 100 mg of 13C-sodiumoctanoate (chemical purity of 99,7 % and an isotopic purity of 99,1 %) at 8 AM. Breath samples, which were expired in close aluminized plastic breath bags of 50 ml content were obtained before substrate administration at baseline and after 10, 20, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 200, 220 and 240 minutes. The subjects were kept in a relaxed sitting position during the octanoate breath test (OBT). Physical activity was restricted during the test. All subjects consumed their test meal within 10 minutes. The 13 C/ 12 C isotope ratio of the breath samples was analysed by isotope-selective nondispersive infrared spectrometer (NDIRS). The results were both expressed as delta (δ) value per mil (‰) and delta over baseline (dob = δ s – δ 0 ). Definition of the δ-value: δ s = (R S /R PDB -1) x 1000 [‰] with R s = 13 C/ 12 C isotope ratio in CO 2 in breath and R PDB = 0.0112372 = isotope ratio in reference (PDB = PeeDeeBelmnite, South Carolina; δ 0 = isotope ratio at baseline).







Mathematical analysis of 13CO2 excretion curves and statistical analysis

As regards the measuring of the proportion of the 13 C-sodium octanoate given by mouth that is metabolised the results were expressed as a percentage dose of 13 C recovered (PDR) over time for each time interval from which the cumulative PDR (cPDR), obtained by numerical integration from PDR values, was calculated for each time interval. This calculation is based on the formula as proposed by Ravussin. [35] CO 2 production rate was assumed as being 300 mmol per unit of body surface area per hour. The body surface area was calculated using the Haycock weight-height formula. [36] The evaluation of the OBT for gastric emptying was done by non-linear regression analysis of the 13 CO 2 -excretion curves (PDR) with the formula PDR(t) = at b e -ct . The expression ln a, as gastric emptying coefficient (GEC) is a reliable parameter to describe the rate at which the stomach empties. The percentage of 13 CO 2 cumulative values was fit using a model given by the formula cPDR(t) = m(1-e -kt ) ß , where y is cPDR at time t in hours and m, k and ß are regression estimated constants, with m being the total amount of 13 CO 2 when time is infinite. Half gastric emptying time (t 50 ) was calculated by taking PDR(t) equal to m/2 in the PDR equation which is expressed as t 50 = (-1/k)ln (1-2 -1/ß ). The Lag phase is expressed as t lag = 1/klnß. [37] Statistical analysis was carried out as a descriptive evaluation of GEC, t 50 (min), tl ag (min) and t peak (min) and characteristics of participants (mean ± SD).







Gastroparesis Cardinal Symptom Index (GCSI) and Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ)

The well-validated Gastroparesis Cardinal Symptom Index (GCSI) was used for clinical evaluation of gastroparesis symptoms. GCSI quantifies nine symptoms in the three different subscales: nausea and vomiting, postprandial fullness, and bloating. [38] In addition patients were asked about the frequency and severity of their stomach complaints, heartburn, burping and nausea symptoms according to the Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ). [39]

The data analysis and statistics were performed by using the commercial software program SPSS statistics 19. All measured parameters and clinical data were first analysed descriptively and they were when presented as mean ± SD. Normality of distribution of the data was tested with the one-sample Kolmogorov-Smirnov test. Data were analyzed using the independent t-test for comparison between HD participants and controls. Pearson correlation analysis was used for exploratory statistical calculations of the normal distributed data.
Results

As expected HD participants had a lower body mass index compared to controls. One HD patient had underweight with a body mass index of 16. There were however, no significant differences between groups concerning any of the clinical data (table 1). Breath test results and clinical data showed normal distribution except for gender.

Results of the 13 C-sodium octanoate breath test are given in table 2. 13 CO 2 -excretion curves (PDR) and the percentage of 13 CO 2 cumulative values (cPDR) showed normal excretion of 13 C. For PDR only PDR max for the maximum amount of 13 CO 2 -excretion reached during testing time is listed in table 2. There were no significant differences compared to controls for the values decisive for the evaluation of gastric emptying, such as PDR max , cPDR, GEC, t 50 (min) and tl ag (min; see table 2). Compared to standard values given in literature, the most important parameters t 50 and tl ag were within normal range (t 50 < 200 min and tl ag <130 min; no data is available in literature for GEC, cPDR and PDR max ) and none of the patients had abnormal breath test results (see figure 1). [24] OBT Parameter Results HD Results Controls PDR max 9.76 ± 2.866.32 – 14.18 9.85 ± 2.615.58 – 14.09 cPDR 23.64 ± 7.92(14.72 – 37.0) 25.38 ± 7.92(15.51 – 34.94) GEC 2.96 ± 0.84(0.95 – 3.77) 2.89 ± 0.36(2.42 – 3.27) t 50 129.26 ± 38.84(77.15 – 197.60) 135.88 ± 22.27(95.74 – 167.47) t lag 85.45 ± 25.14(55.95 – 123.42) 80.74 ± 17.33(56.31 – 109.05) Table 2: 13 C-sodium octanoate breath test results; values are given as mean ± SD; range (min-max) in brackets, Abbreviations: PDR max for the maximum amount of 13 CO 2 -excretion reached during testing time [%]; cPDR – cumulative exhaled 13 CO 2 (cPDR [%]) after 240 minutes; GEC – gastric emptying coefficient; t peak – time to highest exhaled 13 CO 2 value [min]; t 50 – half gastric emptying time [min]; t lag – Lag phase [min]. * – significant differences. Fig. 1: Gastric emptying of solids measured by 13 C sodium octanoate breath test presented as individual lag phase (tl ag ) and gastric half emptying time (t50) in 11 HD participants (controls not shown). The normal t 50 range reported from literature (<200 min) is shown by the dotted line. A normal t lag range is reported to be below 130 min. [24] Gastroparesis Cardinal Symptom Index (GCSI) was 0.3855 (SEM ± 0.48; range 0 – 1.28) and Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) was 0.8182 (SEM ± 1.83; range 0 – 6) for HD participants. Thus, both questionnaire results were in line with published data from healthy controls, without clinical evidence of gastroparesis or dyspepsia. [38][39] GCSI was 0.3027 (SEM ± 0.30; range 0 – 0.83) and SF-LDQ was 2.273 (SEM ± 2.195; range 0 – 7) for controls. Differences were not significant (data not shown). Explorative correlation analysis of breath test results given in table 2 with clinical symptoms from table 1 showed no significant correlation, except for the cognitive sum score and t 50 (p 0.018, r -.692) and tl ag (p 0.019, r -.688), as well as for PDR max and the total functional capacity (TFC; p 0.014, r .712; no analysis of the cognitive subtests was done; see figure 2). Especially no correlation to motor symptoms was found. Fig. 2: A strong relation can be seen between gastric emptying of solids measured by 13 C sodium octanoate breath test A strong relation can be seen between gastric emptying of solids measured by 13 C sodium octanoate breath test, presented as individual t lag (a) and t 50 (b) in minutes and the cognitive sum score of the UHDRS (t 50 – p 0.018; r – .692 and t lag – p 0.019; r – .688), as well as for PDR max (c) and total functional capacity (TFC; p 0.014, r .712). The correlation analysis of GCSI and SF-LDQ with clinical symptoms showed no significant correlation with any of the clinical characteristics from table 1. Discussion Several factors such as dysphagia, an increased motor activity, an increased metabolic rate and hypermetabolic state have been discussed as contributing to weight loss even at early stages of HD. In addition, a recently published study also suggested gastrointestinal tract dysfunction as a reason for weight loss in a Huntington mouse model, similar to findings for Parkinson’s disease (PD). [14][15][21] Several studies describe a delay in gastric emptying for 88% or even for up to 100% of PD patients. [16][17][18][19][20][21] Contrary to this, in our pilot study on HD patients did not provide any evidence of impaired gastric emptying by using a solid meal and the 13 C-sodium octanoate breath test. There were no significant differences compared to controls and also compared to standard values given in literature all parameters were within normal range. In addition, we had no clinical evidence of gastroparesis or dyspepsia symptoms by using the “Gastroparesis Cardinal Symptom Index” and “Short-Form Leeds Dyspepsia Questionnaire” in our cohort. Thus, our data contrast with data for PD, but also with data for HD mice. As a possible explanation, gastric emptying may only contribute to weight loss more severe stages of HD. R6/2 HD mice usually show a very rapid course of the disease. A recent published study investigating the GI tract in a R6/2 mice model carrying a mean of 204 CAG-repeats describes several GI abnormalities, including an increased water content in R6/2 compared to feces in wild type mice from 8 weeks of age. The fecal output as a percentage of food intake however, was only significantly increased at 12 weeks, but not at 8 weeks. [14] This indicates that the occurrence of malabsorption of nutrients plays an important role in weight loss in HD mice only in the end stage. The study did not investigate early stages of the disease prior 8 weeks in the mice model. An earlier study from our group describes a high prevalence of gastritis or esophagitis as an accidental finding during PEG-placement, as a possible indication of gastrointestinal tract dysfunction in HD patients at advanced stages of the disease. [40] The findings in this study were also correlated with the duration and severity of the disease, also suggesting that gastrointestinal tract dysfunction might occur later in the course of the disease. We presumed that influences from the disease itself as well as secondary mechanisms like medication and general disability may contribute. [40] It was also the case in this study that the focus was not on early symptomatic patients. To summarize, the pilot data from our study suggest that impaired gastric emptying is not an early event in HD when compared to PD. We can not exclude that gastric emptying contributes to weight loss at more advanced stages of the disease. Surprisingly, we found a significant correlation for the cognitive sum score und the total functional capacity of the UHDRS and breath test results, such as t 50 (47.8% of variance), tl ag (47.4% of variance) and PDR max which usually shows the most precise quantification (50.6% of variance; see figure 2). This was not expected, since OBT results were within normal range. Cognitive decline, however, is a very early event in the course of HD. [41] In fact the cognitive sum score from our HD participants showed a broad range from 98-346 points with a mean of 195.1 points indicating a cognitive impairment in most of the patients. It is well known that the performance in UHDRS cognitive tests declined during disease progression, as did the functional capacity (TFC), which is highly dependent on cognitive tasks. [42][43] A decrement in mitochondrial function is discussed as contributing to age-dependent functional deficits in neurons and myocytes in normal aging and other neurological disorders, such as Alzheimer’s disease, accompanied with a cognitive decline. [44][45][46] Mitochondrial dysfunction is well known in HD and seems to be a relevant and early feature in the pathology. [47][48][49] Mutant htt (mtHtt) tends to aggregate in cytoplasm and nucleus of neurons as well as non-neuronal tissues including the liver. [50][51][52][53][54][55] Within the mitochondria, octanoic acid undergoes b-oxidation. Octanic acid generates acetyl coenzyme A which enters the Krebs cycle and is oxidized to CO 2 . Therefore breath tests based on octanoate, usually used to assess gastric emptying, should also reflect mitochondrial function. [56] Thus, one can speculate that a correlation of OBT results with results of cognitive tasks might reflect a parallel decline in cognitive and mitochondrial function. To our knowledge this is the first study dealing with gastrointestinal track dysfunction in HD in vivo. A limitation of our study is the relative small number of participants. To exclude drug effects we only included patients without any medication and without serious comorbidities. On the other hand, due to the fact that this is a very rare group of patients it is a strength of our study that we can exclude medication effects. Competing interests The authors declare that they have no competing interests. Ethics The local ethics committee of the university approved this study. Acknowledgements We are grateful to all patients for participation. References Djousse L, Knowlton B, Cupples LA, Marder K, Shoulson I, Myers RH. Weight loss in early stage of Huntington's disease. Neurology 2002;59:1325-1330. Sanberg PR, Fibiger HC, Mark RF. Body weight and dietary factors in Huntington's disease patients compared with matched controls. Med J Aust 1981;1:407-409. Trejo A, Tarrats RM, Alonso ME, Boll MC, Ochoa A, Velasquez L. Assessment of the nutrition status of patients with Huntington's disease. Nutrition 2004;20:192-196. Goodman AO, Murgatroyd PR, Medina-Gomez G, et al. The metabolic profile of early Huntington's disease--a combined human and transgenic mouse study. Exp Neurol 2008;210:691-698. Mochel F, Charles P, Seguin F, et al. Early energy deficit in Huntington disease: identification of a plasma biomarker traceable during disease progression. PLoS One 2007;2:e647. Hamilton JM, Wolfson T, Peavy GM, Jacobson MW, Corey-Bloom J. Rate and correlates of weight change in Huntington's disease. J Neurol Neurosurg Psychiatry 2004;75:209-212. Nance MA, Sanders G. Characteristics of individuals with Huntington disease in long-term care. Mov Disord 1996;11:542-548. Gaba AM, Zhang K, Marder K, Moskowitz CB, Werner P, Boozer CN. Energy balance in early-stage Huntington disease. Am J Clin Nutr 2005;81:1335-1341. Mahant N, McCusker EA, Byth K, Graham S. Huntington's disease: clinical correlates of disability and progression. Neurology 2003;61:1085-1092. Pratley RE, Salbe AD, Ravussin E, Caviness JN. Higher sedentary energy expenditure in patients with Huntington's disease. Ann Neurol 2000;47:64-70. van der Burg JM, Bacos K, Wood NI, et al. Increased metabolism in the R6/2 mouse model of Huntington's disease. Neurobiol Dis 2008;29:41-51. Weydt P, Pineda VV, Torrence AE, et al. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab 2006;4:349-362. Aziz NA, van der Burg JM, Landwehrmeyer GB, Brundin P, Stijnen T, Roos RA. Weight loss in Huntington disease increases with higher CAG repeat number. Neurology 2008;71:1506-1513. van der Burg JM, Winqvist A, Aziz NA, et al. Gastrointestinal dysfunction contributes to weight loss in Huntington's disease mice. Neurobiol Dis;44:1-8. Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Parkinsonism Relat Disord;17:10-15. Goetze O, Nikodem AB, Wiezcorek J, et al. Predictors of gastric emptying in Parkinson's disease. Neurogastroenterol Motil 2006;18:369-375. Goetze O, Wieczorek J, Mueller T, Przuntek H, Schmidt WE, Woitalla D. Impaired gastric emptying of a solid test meal in patients with Parkinson's disease using 13C-sodium octanoate breath test. Neurosci Lett 2005;375:170-173. Muller T, Erdmann C, Bremen D, et al. Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease patients. Clin Neuropharmacol 2006;29:61-67. Woitalla D, Goetze O. Treatment approaches of gastrointestinal dysfunction in Parkinson's disease, therapeutical options and future perspectives. J Neurol Sci. Djaldetti R, Baron J, Ziv I, Melamed E. Gastric emptying in Parkinson's disease: patients with and without response fluctuations. Neurology 1996;46:1051-1054. Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol 2003;2:107-116. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 2003;24:197-211. Andrich J, Schmitz T, Saft C, et al. Autonomic nervous system function in Huntington's disease. J Neurol Neurosurg Psychiatry 2002;72:726-731. Keller J, Franke A, Storr M, Wiedbrauck F, Schirra J. [Clinically relevant breath tests in gastroenterological diagnostics--recommendations of the German Society for Neurogastroenterology and Motility as well as the German Society for Digestive and Metabolic Diseases]. Z Gastroenterol 2005;43:1071-1090. Shoulson I. Huntington disease: functional capacities in patients treated with neuroleptic and antidepressant drugs. Neurology 1981;31:1333-1335. Huntington Study Group. Unified Huntington's Disease Rating Scale: reliability and consistency. Mov Disord 1996;11:136-142. Andrich J, Saft C, Ostholt N, Muller T. Assessment of simple movements and progression of Huntington's disease. J Neurol Neurosurg Psychiatry 2007;78:405-407. Andrich J, Saft C, Ostholt N, Muller T. Complex movement behaviour and progression of Huntington's disease. Neurosci Lett 2007;416:272-274. Saft C, Andrich J, Meisel NM, Przuntek H, Muller T. Assessment of simple movements reflects impairment in Huntington's disease. Mov Disord 2006;21:1208-1212. Saft C, Andrich J, Meisel NM, Przuntek H, Muller T. Assessment of complex movements reflects dysfunction in Huntington's disease. J Neurol 2003;250:1469-1474. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561-571. Penney JB, Jr., Vonsattel JP, MacDonald ME, Gusella JF, Myers RH. CAG repeat number governs the development rate of pathology in Huntington's disease. Ann Neurol 1997;41:689-692. Muller T, Woitalla D, Goetze O, Erdmann C. Entacapone improves absorption of a coadministered salt in patients with Parkinson's disease. Mov Disord 2008;23:1458-1461. Ravussin E, Pahud P, Thelin-Doerner A, Arnaud MJ, Jequier E. Substrate utilization during prolonged exercise after ingestion of 13C-glucose in obese and control subjects. Int J Obes 1980;4:235-242. Haycock GB, Schwartz GJ, Wisotsky DH. Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr 1978;93:62-66. Ghoos YF, Maes BD, Geypens BJ, et al. Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test. Gastroenterology 1993;104:1640-1647. Revicki DA, Rentz AM, Dubois D, et al. Development and validation of a patient-assessed gastroparesis symptom severity measure: the Gastroparesis Cardinal Symptom Index. Aliment Pharmacol Ther 2003;18:141-150. Fraser A, Delaney BC, Ford AC, Qume M, Moayyedi P. The Short-Form Leeds Dyspepsia Questionnaire validation study. Aliment Pharmacol Ther 2007;25:477-486. Andrich JE, Wobben M, Klotz P, Goetze O, Saft C. Upper gastrointestinal findings in Huntington's disease: patients suffer but do not complain. J Neural Transm 2009;116:1607-1611. Stout JC, Paulsen JS, Queller S, et al. Neurocognitive signs in prodromal Huntington disease. Neuropsychology;25:1-14. Beglinger LJ, Duff K, Allison J, et al. Cognitive change in patients with Huntington disease on the Repeatable Battery for the Assessment of Neuropsychological Status. J Clin Exp Neuropsychol 2010;32:573-578. Beglinger LJ, O'Rourke JJ, Wang C, Langbehn DR, Duff K, Paulsen JS. Earliest functional declines in Huntington disease. Psychiatry Res;178:414-418. Bishop NA, Lu T, Yankner BA. Neural mechanisms of ageing and cognitive decline. Nature 2010;464:529-535. Glade MJ. Oxidative stress and cognitive longevity. Nutrition 2010;26:595-603. Sultana R, Butterfield DA. Oxidatively modified, mitochondria-relevant brain proteins in subjects with Alzheimer disease and mild cognitive impairment. J Bioenerg Biomembr 2009;41:441-446. Bossy-Wetzel E, Petrilli A, Knott AB. Mutant huntingtin and mitochondrial dysfunction. Trends Neurosci 2008;31:609-616. Saft C, Zange J, Andrich J, et al. Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's disease. Mov Disord 2005;20:674-679. Taherzadeh-Fard E, Saft C, Akkad DA, et al. PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic modifiers of Huntington disease. Mol Neurodegener;6:32. Sassone J, Colciago C, Cislaghi G, Silani V, Ciammola A. Huntington's disease: the current state of research with peripheral tissues. Exp Neurol 2009;219:385-397. Browne SE. Mitochondria and Huntington's disease pathogenesis: insight from genetic and chemical models. Ann N Y Acad Sci 2008;1147:358-382. Davies SW, Turmaine M, Cozens BA, et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 1997;90:537-548. Sathasivam K, Hobbs C, Turmaine M, et al. Formation of polyglutamine inclusions in non-CNS tissue. Hum Mol Genet 1999;8:813-822. Scherzinger E, Lurz R, Turmaine M, et al. Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 1997;90:549-558. Squitieri F, Cannella M, Sgarbi G, et al. Severe ultrastructural mitochondrial changes in lymphoblasts homozygous for Huntington disease mutation. Mech Ageing Dev 2006;127:217-220. Grattagliano I, Lauterburg BH, Palasciano G, Portincasa P. 13C-breath tests for clinical investigation of liver mitochondrial function. Eur J Clin Invest;40:843-850."

The Brain in Your Gut

I know a lot of people with gastroparesis have memory issues, myself included. So, what causes this? How does our brain chemistry change when you have gastroparesis? Sleep deprivation, malnutrition, and medication can play a big part in altering our brain chemistry but I wanted to dig a bit deeper to see what else can change our body's brain chemistry, and why it affects us so harshly.

Credit: ISTOCKPHOTO/ERAXION


According to Cal Tech http://www.caltech.edu/news/microbes-help-produce-serotonin-gut-46495,

"Although serotonin is well known as a brain neurotransmitter, it is estimated that 90 percent of the body's serotonin is made in the digestive tract. In fact, altered levels of this peripheral serotonin have been linked to diseases such as irritable bowel syndrome, cardiovascular disease, and osteoporosis.

'More and more studies are showing that mice or other model organisms with changes in their gut microbes exhibit altered behaviors,' explains Elaine Hsiao, research assistant professor of biology and biological engineering and senior author of the study. 'We are interested in how microbes communicate with the nervous system. To start, we explored the idea that normal gut microbes could influence levels of neurotransmitters in their hosts.'

Peripheral serotonin is produced in the digestive tract by enterochromaffin (EC) cells and also by particular types of immune cells and neurons. Hsiao and her colleagues first wanted to know if gut microbes have any effect on serotonin production in the gut and, if so, in which types of cells. They began by measuring peripheral serotonin levels in mice with normal populations of gut bacteria and also in germ-free mice that lack these resident microbes.

The researchers found that the EC cells from germ-free mice produced approximately 60 percent less serotonin than did their peers with conventional bacterial colonies. When these germ-free mice were recolonized with normal gut microbes, the serotonin levels went back up—showing that the deficit in serotonin can be reversed.

'EC cells are rich sources of serotonin in the gut. What we saw in this experiment is that they appear to depend on microbes to make serotonin—or at least a large portion of it,' says Jessica Yano, first author on the paper and a research technician working with Hsiao.

The researchers next wanted to find out whether specific species of bacteria, out of the diverse pool of microbes that inhabit the gut, are interacting with EC cells to make serotonin.

After testing several different single species and groups of known gut microbes, Yano, Hsiao, and colleagues observed that one condition—the presence of a group of approximately 20 species of spore-forming bacteria—elevated serotonin levels in germ-free mice. The mice treated with this group also showed an increase in gastrointestinal motility compared to their germ-free counterparts, and changes in the activation of blood platelets, which are known to use serotonin to promote clotting.

Wanting to home in on mechanisms that could be involved in this interesting collaboration between microbe and host, the researchers began looking for molecules that might be key. They identified several particular metabolites—products of the microbes' metabolism—that were regulated by spore-forming bacteria and that elevated serotonin from EC cells in culture. Furthermore, increasing these metabolites in germ-free mice increased their serotonin levels.

Previous work in the field indicated that some bacteria can make serotonin all by themselves. However, this new study suggests that much of the body's serotonin relies on particular bacteria that interact with the host to produce serotonin, says Yano. 'Our work demonstrates that microbes normally present in the gut stimulate host intestinal cells to produce serotonin,' she explains.

'While the connections between the microbiome and the immune and metabolic systems are well appreciated, research into the role gut microbes play in shaping the nervous system is an exciting frontier in the biological sciences,' says Sarkis K. Mazmanian, Luis B. and Nelly Soux Professor of Microbiology and a coauthor on the study. 'This work elegantly extends previous seminal research from Caltech in this emerging field'.

Additional coauthor Rustem Ismagilov, the Ethel Wilson Bowles and Robert Bowles Professor of Chemistry and Chemical Engineering, adds, 'This work illustrates both the richness of chemical interactions between the hosts and their microbial communities, and Dr. Hsiao's scientific breadth and acumen in leading this work.'

Serotonin is important for many aspects of human health, but Hsiao cautions that much more research is needed before any of these findings can be translated to the clinic.

'We identified a group of bacteria that, aside from increasing serotonin, likely has other effects yet to be explored,' she says. 'Also, there are conditions where an excess of peripheral serotonin appears to be detrimental.'

Although this study was limited to serotonin in the gut, Hsiao and her team are now investigating how this mechanism might also be important for the developing brain. 'Serotonin is an important neurotransmitter and hormone that is involved in a variety of biological processes. The finding that gut microbes modulate serotonin levels raises the interesting prospect of using them to drive changes in biology,' says Hsiao.

The work was published in an article titled 'Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis.' In addition to Hsiao, Yano, Mazmanian, and Ismagilov, other Caltech coauthors include undergraduates Kristie Yu, Gauri Shastri, and Phoebe Ann; graduate student Gregory Donaldson; postdoctoral scholar Liang Ma. Additional coauthor Cathryn Nagler is from the University of Chicago."

Image Credit: http://i2.wp.com/sitn.hms.harvard.edu/wp-content/uploads/2016/08/Gut-Brain-Microbe-Figures_FINAL.png





This is an interesting study considering that Gastroparesis/DTP is slow to little to no motility, depending on how severe it is in each person affected with it. If 90 percent of serotonin is produced in the stomach, what happens to that serotonin when the motility is limited or the stomach is removed? Could that be a link to depression in people with Gastroparesis? Scientific American believes that psychiatry may have to readjust to consider just that in the years to come as discussed below.



According to Scientific American https://www.scientificamerican.com/article/gut-second-brain/,

"As Olympians go for the gold in Vancouver, even the steeliest are likely to experience that familiar feeling of 'butterflies' in the stomach. Underlying this sensation is an often-overlooked network of neurons lining our guts that is so extensive some scientists have nicknamed it our 'second brain'.

A deeper understanding of this mass of neural tissue, filled with important neurotransmitters, is revealing that it does much more than merely handle digestion or inflict the occasional nervous pang. The little brain in our innards, in connection with the big one in our skulls, partly determines our mental state and plays key roles in certain diseases throughout the body.

Although its influence is far-reaching, the second brain is not the seat of any conscious thoughts or decision-making.

'The second brain doesn't help with the great thought processes…religion, philosophy and poetry is left to the brain in the head,' says Michael Gershon, chairman of the Department of Anatomy and Cell Biology at New York–Presbyterian Hospital/Columbia University Medical Center, an expert in the nascent field of neurogastroenterology and author of the 1998 book The Second Brain (HarperCollins).

Technically known as the enteric nervous system, the second brain consists of sheaths of neurons embedded in the walls of the long tube of our gut, or alimentary canal, which measures about nine meters end to end from the esophagus to the anus. The second brain contains some 100 million neurons, more than in either the spinal cord or the peripheral nervous system, Gershon says.

This multitude of neurons in the enteric nervous system enables us to 'feel' the inner world of our gut and its contents. Much of this neural firepower comes to bear in the elaborate daily grind of digestion. Breaking down food, absorbing nutrients, and expelling of waste requires chemical processing, mechanical mixing and rhythmic muscle contractions that move everything on down the line.

Thus equipped with its own reflexes and senses, the second brain can control gut behavior independently of the brain, Gershon says. We likely evolved this intricate web of nerves to perform digestion and excretion 'on site,' rather than remotely from our brains through the middleman of the spinal cord. 'The brain in the head doesn't need to get its hands dirty with the messy business of digestion, which is delegated to the brain in the gut,' Gershon says. He and other researchers explain, however, that the second brain's complexity likely cannot be interpreted through this process alone.

'The system is way too complicated to have evolved only to make sure things move out of your colon,' says Emeran Mayer, professor of physiology, psychiatry and biobehavioral sciences at the David Geffen School of Medicine at the University of California, Los Angeles (U.C.L.A.). For example, scientists were shocked to learn that about 90 percent of the fibers in the primary visceral nerve, the vagus, carry information from the gut to the brain and not the other way around. "Some of that info is decidedly unpleasant," Gershon says.

The second brain informs our state of mind in other more obscure ways, as well. 'A big part of our emotions are probably influenced by the nerves in our gut,' Mayer says. Butterflies in the stomach—signaling in the gut as part of our physiological stress response, Gershon says—is but one example. Although gastrointestinal (GI) turmoil can sour one's moods, everyday emotional well-being may rely on messages from the brain below to the brain above. For example, electrical stimulation of the vagus nerve—a useful treatment for depression—may mimic these signals, Gershon says.

Given the two brains' commonalities, other depression treatments that target the mind can unintentionally impact the gut. The enteric nervous system uses more than 30 neurotransmitters, just like the brain, and in fact 95 percent of the body's serotonin is found in the bowels. Because antidepressant medications called selective serotonin reuptake inhibitors (SSRIs) increase serotonin levels, it's little wonder that meds meant to cause chemical changes in the mind often provoke GI issues as a side effect. Irritable bowel syndrome—which afflicts more than two million Americans—also arises in part from too much serotonin in our entrails, and could perhaps be regarded as a "mental illness" of the second brain.

Scientists are learning that the serotonin made by the enteric nervous system might also play a role in more surprising diseases: In a new Nature Medicine study published online February 7, a drug that inhibited the release of serotonin from the gut counteracted the bone-deteriorating disease osteoporosis in postmenopausal rodents. (Scientific American is part of Nature Publishing Group.) 'It was totally unexpected that the gut would regulate bone mass to the extent that one could use this regulation to cure—at least in rodents—osteoporosis,' says Gerard Karsenty, lead author of the study and chair of the Department of Genetics and Development at Columbia University Medical Center.

Serotonin seeping from the second brain might even play some part in autism, the developmental disorder often first noticed in early childhood. Gershon has discovered that the same genes involved in synapse formation between neurons in the brain are involved in the alimentary synapse formation. 'If these genes are affected in autism,' he says, 'it could explain why so many kids with autism have GI motor abnormalities' in addition to elevated levels of gut-produced serotonin in their blood.

Down the road, the blossoming field of neurogastroenterology will likely offer some new insight into the workings of the second brain—and its impact on the body and mind. 'We have never systematically looked at [the enteric nervous system] in relating lesions in it to diseases like they have for the' central nervous system, Gershon says. One day, perhaps there will be well-known connections between diseases and lesions in the gut's nervous system as some in the brain and spinal cord today indicate multiple sclerosis.

Cutting-edge research is currently investigating how the second brain mediates the body's immune response; after all, at least 70 percent of our immune system is aimed at the gut to expel and kill foreign invaders.

U.C.L.A.'s Mayer is doing work on how the trillions of bacteria in the gut 'communicate' with enteric nervous system cells (which they greatly outnumber). His work with the gut's nervous system has led him to think that in coming years psychiatry will need to expand to treat the second brain in addition to the one atop the shoulders."

Image Credit: http://fitlife.tv/wp-content/uploads/2015/06/Gut-System.bmp






According to John's Hopkins http://www.hopkinsmedicine.org/health/healthy_aging/healthy_body/the-brain-gut-connection,

"If you’ve ever "gone with your gut' to make a decision or felt 'butterflies in your stomach' when nervous, you’re likely getting signals from an unexpected source: your second brain. Hidden in the walls of the digestive system, this 'brain in your gut' is revolutionizing medicine’s understanding of the links between digestion, mood, health and even the way you think.

Scientists call this little brain the enteric nervous system (ENS). And it’s not so little. The ENS is two thin layers of more than 100 million nerve cells lining your gastrointestinal tract from esophagus to rectum.



What Does Your Gut’s Brain Control?

Unlike the big brain in your skull, the ENS can’t balance your checkbook or compose a love note. 'Its main role is controlling digestion, from swallowing to the release of enzymes that break down food to the control of blood flow that helps with nutrient absorption to elimination,' explains Jay Pasricha, M.D., director of the Johns Hopkins Center for Neurogastroenterology, whose research on the enteric nervous system has garnered international attention. 'The enteric nervous system doesn’t seem capable of thought as we know it, but it communicates back and forth with our big brain—with profound results.'

The ENS may trigger big emotional shifts experienced by people coping with irritable bowel syndrome (IBS) and functional bowel problems such as constipation, diarrhea, bloating, pain and stomach upset. 'For decades, researchers and doctors thought that anxiety and depression contributed to these problems. But our studies and others show that it may also be the other way around,' Pasricha says. Researchers are finding evidence that irritation in the gastrointestinal system may send signals to the central nervous system (CNS) that trigger mood changes.

'These new findings may explain why a higher-than-normal percentage of people with IBS and functional bowel problems develop depression and anxiety,' Pasricha says. 'That’s important, because up to 30 to 40 percent of the population has functional bowel problems at some point.'



New Gut Understanding Equals New Treatment Opportunities

This new understanding of the ENS-CNS connection helps explain the effectiveness of IBS and bowel-disorder treatments such as antidepressants and mind-body therapies like cognitive behavioral therapy (CBT) and medical hypnotherapy. 'Our two brains ‘talk’ to each other, so therapies that help one may help the other,' Pasricha says. 'In a way, gastroenterologists (doctors who specialize in digestive conditions) are like counselors looking for ways to soothe the second brain.'

Gastroenterologists may prescribe certain antidepressants for IBS, for example—not because they think the problem is all in a patient’s head, but because these medications calm symptoms in some cases by acting on nerve cells in the gut, Pasricha explains. 'Psychological interventions like CBT may also help to 'improve communications' between the big brain and the brain in our gut,' he says.



Still More to Learn About Mind-Gut Link

Pasricha says research suggests that digestive-system activity may affect cognition (thinking skills and memory), too. 'This is an area that needs more research, something we hope to do here at Johns Hopkins,' he says.

Another area of interest: Discovering how signals from the digestive system affect metabolism, raising or reducing risk for health conditions like type 2 diabetes. 'This involves interactions between nerve signals, gut hormones and microbiota—the bacteria that live in the digestive system,'Pasricha says."

Image Credit: https://www.lotronex.com/Images/Patient-MOA_1.jpg




According to Neurology Advisor,

"Recently, evidence has accumulated to support a complex neurobiologic basis for migraine, with origins beyond the brain. The prevailing theory involves the gut-brain axis, which postulates a complex interplay between the brain and the gastrointestinal tract. However, the precise mechanism that links the brain and the gut and triggers a migraine event remains unclear."

Read more about it here: http://www.neurologyadvisor.com/migraine-and-headache/what-we-know-association-between-migraine-gastrointestinal-health/article/695858/

Image Source: The Smithsonian.









According to The Smithsonian,

"The human microbiome—a collection of bacteria, archaea, fungi and viruses commingling in the gut and intestines—has been linked to a wide range of human health conditions, including digestive health and the prevention of autoimmune diseases. Some research has even identified a possible link between gut health and brain function. Building on this work, a study published yesterday in Nature Microbiology reveals that clinical depression could be affected by the amounts of certain bacteria in the gut.

The research team, led by microbiologist Jeroen Raes of the Catholic University of Leuven in Belgium, found that almost all gut bacteria are able to produce neurotransmitters, which are chemicals like dopamine and serotonin that enable communication between neurons. If these 'chemical messengers' are sent to receptors in the brain, they can influence mood and behavior. The researchers also identified two strains of bacteria that are lacking in the guts of people who have been diagnosed with depression.

The study adds to mounting evidence that an association between gut health and the brain exists. However, it does not establish whether poor mental health causes depletion of the bacteria, or if the missing bacteria intensifies symptoms associated with mood disorders. More research is needed to conclusively say that gut bacteria influences mental health, says Mark Lyte, a professor of microbiology at Iowa State University who wasn’t involved in the study.

'The studies are just really starting,' Lyte says. 'We do not fully understand what all the genes in all the bacteria do, so don't make the conclusion that we understand everything about the microbiota in terms of their genetic capacity to make [neurotransmitters]. We only understand a fraction of that.' Scientists recently identified more than 100 new species of bacteria in the human gut, underscoring how much we still have to learn about the functions of the microbiome.

Raes and his team studied the gut bacteria of over 2,000 European participants to examine a possible link between the microbiome and mental health. In their study, the team tested the genomes of 532 strains of bacteria to determine if the bacteria could create neurotransmitters. Over 90 percent of the bacteria in the study demonstrated the ability to produce one or more of these chemical messengers.

The body’s longest nerve, the vagus nerve, runs from the brainstem to the lowest part of the intestines. The nerve is thought to be a two-way highway, sending signals from the brain to the gut to regulate digestion and bringing signals from the gut to the brain. The latter function provides a possible pathway for neurotransmitters produced by gut bacteria to influence mental health, Raes says. The team found that both Coprococcus and Dialister bacteria were depleted among individuals with depression, even when controlling for the effects of antidepressants. Coprococcus was also found to have a biological pathway associated with dopamine, a neurotransmitter known to influence mental health.

The next step, Lyte says, is to develop a more complete understanding of how these two strains of bacteria function in the gut. Scientists have studied the genetic traits of some bacteria extensively, like E. Coli, but the genomes and traits of bacteria like Coprococcus and Dialister have yet to be carefully examined. Lyte says that scientists will need to use 'old-school' microbiology, growing these bugs in petri dishes to see how they function. A bacterium that behaves one way on paper could function very differently when exposed to a diverse environment of microbes similar to the human gut.

'You have to grow these bugs up and see what they do [in different environments] to understand what they’re going to do when they’re in the host,' Lyte says.

Additionally, Raes says his team has only identified bacteria that could influence mental health at the genus level, and that it’s crucial to identify the specific species of bacteria that are absent in people with depression to test a possible relationship between the gut and the brain. While lower levels of Dialister were associated with depression, a recent paper linked higher levels of Dialister with arthritis. It could be that prevalence of one species of Dialister increases risk of arthritis while prevalence of another reduces risk of depression, Raes says, but determining such specifics will require additional studies.

The ability to produce neurotransmitters also might be unique to bacteria that evolved in the gut, as the capability hasn’t been found in wild bacteria outside the microbiome. 'It feels like an evolutionary adaptation to the symbiosis of bacteria and [humans],' Raes says. 'If you start thinking about that, then your head explodes. Bacteria live within us and have found all these ways to communicate with us and potentially influence our behavior.'

Emma Allen-Vercoe, a professor of microbiology at the University of Guelph in Ontario, says she is excited about the future potential of microbiome research. While many more studies would be required before scientists could perform a treatment trial, Allen-Vercoe believes that Coprococcus and Dialister could be great candidates to use as psychobiotics, or probiotics that target mental health. Finding a way to grow these microbes so they could be administered to patients would be 'far from trivial,' but she hopes scientists can eventually introduce the bacteria into human guts of and examine the results.

'When I read this paper I was super excited, because I really think this is a new frontier in medicine,' Allen-Vercoe says. 'Thinking outside the box in terms of using microbes in the gut to treat diseases that traditionally haven’t been associated with the gut is quite exciting, because we’re thinking about things in a whole different way. They’ve really started something here.'"

Thank you, to one of our group members, Sarah L., for bringing the article above to my attention! I really appreciate it!



So, the brain in your gut can affect your memory. It makes me think that if you have little or no motility, it could contribute to memory loss, in addition to other things like sleep deprivation, malnutrition, and medication. It seems like a lot of issues can cause memory loss in those who suffer from Gastroparesis/DTP. Personally, I have to carry around a journal to write things in because I forget a lot of things. More research is going into this, so hopefully, we will have answers soon.

Gastric Endoscopic Myotomy Showing Promise for Gastroparesis

This is an article copied from: http://www.medscape.com/viewarticle/863847#vp_1. I like to go back and read interesting breakthroughs when it comes back to gastroparesis treatment. Also, if you have had this procedure done, please email me your story: emilysstomach[at[gmail.com and I will include your story in this article, and whether it did or didn't work for you to let other GPers know. So far, the only clinic I know that does this procedure is Emory in Atlanta, GA.

Gastric Endoscopic Myotomy Showing Promise for Gastroparesis
By: Caroline Helwick
May 25, 2016

FDA Approves Gastroparesis Test for Any Clinical Setting
Nortriptyline Minimal Benefit in Gastroparesis
Ghrelin Receptor Agonist Improves Diabetic Gastroparesis
RELATED DRUGS & DISEASES
Kidney-Pancreas Transplantation
All nine of the study patients were refractory to conventional treatment — including gastric electrical stimulation in two patients — for at least 6 months, had severe symptoms, had been hospitalized at least twice in the previous 6 months, and had disturbed gastric emptying.

Mean procedural time was 48 minutes. There were no peri- or postoperative complications, and all patients could eat 2 days after surgery and were discharged by day 5.

Clinical efficacy was very high; 85% of the patients had improved significantly after 1 month. One of the failures was a recurrence at 2 months in a diabetic patient with renal insufficiency.

Gastroparesis Cardinal Symptom Index (CGSI) score decreased from 3.5 before the procedure to 0.9 at 1 month (P < .001) and 1.1 at 3 months (P < .001). Improvements were also significant for nausea, vomiting, abdominal pain, gastric fullness, and early satiety at 3 months (P <.001 for all), but not for anorexia. Time to half gastric emptying was significantly better after the procedure than before (133 vs 222 minutes; P < .001). Improved quality of life was reported by 63% of patients. Table. Gastric Emptying Mean Residual Percentage Before G-POEM, % After G-POEM, % P Value At 2 hours 76 40 <.001 At 4 hours 44 19 NS Dr Gonzalez acknowledged that long-term follow-up is needed for these patients, as are prospective studies, which his group has initiated. Dr Khashab said G-POEM can be considered not only for patients with recurrent hospitalizations, but also "for any patient with nausea and vomiting that significantly affects their quality of life, even without hospitalization." Although some patients respond to simple medical therapy, metoclopramide carries a black-box warning for tardive dyskinesia "and is only marginally effective," and antiemetics provide only symptomatic relief, Dr Khashab pointed out. Before attempting G-POEM, endoscopists should be skilled at esophageal POEM, he added. Dr Gonzalez offered a few procedural tips: "Start at the 5 o'clock position from the pylorus, keep checking your direction, and stop at the pyloric arch." Dr John Vargo These results come from small case series, but they show "intriguingly positive results" in terms of symptomatic response and gastric emptying tests, said John Vargo, MD, from the Cleveland Clinic's Digestive Disease and Surgery Institute. "G-POEM is definitely something we have to look at," Dr Vargo Medscape Medical News. "For these patients, pharmacologic treatments are imperfect; medications have many different side effects. We do have another avenue with gastric pacing, but again, this approach is in its infancy." "I'm hopeful G-POEM will help these very sick people who have a very challenged quality of life," he said. "It's good to see these results, and I look forward to longer follow-up and a larger series of patients." Dr Khashab, Dr Gonzalez, and Dr Vargo have disclosed no relevant financial relationships. Digestive Disease Week (DDW) 2016: Abstracts Mo2015 and 715. Presented May 23, 2016.

Gastroparesis and Me + Mayo Clinic Updates

I logged into Facebook today and got a really nice surprise. Tanya, from GASTROPARESIS AND ME posted this,

Gastroparesis is not something to turn away from. This digestive disease doesn't care what you have planned for your life. GP does what it can to debilitate, destroy, torture, and wreak havoc in any way it can. http://www.GastroparesisAndME.com/ for medical links and personal stories, as well as support from others like Emily and her effort to support others with GP. Thank you Em for all you do!!!

It wasn't over yet. She contacted me and asked me if I could help out her organization. I was elated! Tanya does really great things in the Gastroparesis community like trying to get legislation passed for Gastroparesis, updated medical news, and trying to spread awareness. I agreed, because it's an honor to work with her. I am not an admin of her GASTROPARESIS AND ME FACEBOOK GROUP as well as an admin on GASTROPARESIS AND ME'S TWITTER ACCOUNT. I'm currently working on trying to get her more "likes" on Facebook. She had 200ish when I started working on her page a few hours ago and it just hit 245. I hope more people will like her page because what she does is very important.

She also linked my blog along with LaShelle's from her website (posted above in the second sentence). You can click Emily's Stomach on her website and it will take you directly to my blog. I am really excited about that! When I started my blog, I never knew it would be this popular! I'm amazed and dazzled by all of you who read it. You really help me in ways you might never know. <3 I'm also working with another group that will eventually become a non-profit for gastroparesis but I can't talk about it right now. I'll announce it when it finally happens and we can all celebrate together! I finally heard from the Mayo Clinic. They set up appointments for me the first week of May. On the first day that I'm there, they're going to put a small tube down my nose and into my throat. Here's the diagram that came with my schedule:


I'm a bit nervous because they are going to do it while I'm awake, using numbing spray on my throat. I've been vomiting so violently and so much that I'm scared I'm going to vomit all over the person who is sticking that down my throat. The doctor wants to know if I'm vomiting up stomach acid. He has a suspicion that the acid is making the motility problems worse. I'll know more once the test is completed and I meet with him the day after. He mentioned stomach surgery before if the medication didn't work. I'm nervous but mainly I just want some answers so that I can go back to school in the fall. I can't take labs vomiting as much as I am now.

I took a picture of myself yesterday during a GP Attack that hasn't let up yet. So here is the Emo picture I took during my attack:



Overall, despite being ill, I've had a pretty good day full of good news. I'm very thankful for my friends and family. They lift me up when I feel discouraged. I did yesterday and everyone on Facebook tried to cheer me up - and it worked. I went to bed smiling.

My blog has had over 14,000 views! I can't thank you enough for reading. When I started this blog, I did it to keep track of my medical journey, tests, and hospital visits. I decided to write to help others through my own experiences - especially unnecessary tests. My blog has continued to evolve and I get messages telling me how much my blog has helped people. I want to say thank you. When I'm isolated at home because of GP, I can still feel productive and useful. I've always wanted to help others and I've always wanted to be a writer. I just never imagined that I would be a writer about a little understood and known illness.

IBS Specialist or Gastroenterologist - What's the Difference?

IBS Specialist or Gastroenterologist: What’s the Difference?

**note: I wanted to thank Melissa "Missy" Culp for finding these articles and for asking intriguing questions on the Gastroparesis Facebook Page. She was my inspiration for my article, so I would like to name her a co-author.



There are IBS Specialists and there are Gastroenterologists.

IBS specialists are experts in IRRITABLE BOWEL SYNDROME (IBS). A gastroenterologist may diagnose IBS, but that will only tell you what you already know, that your bowel irritates you.

To the IBS specialist the label of IBS only serves as a starting point for further investigation, nothing more. The IBS specialist focuses on assessing and diagnosing the cause of your digestive problems, not on the gross structural integrity of the digestive tract. Rather than focusing on the patients symptoms, or simply treating the symptoms, the IBS specialist is devoted to identifying the condition or conditions in the patient that are causing the symptoms.



What Exactly Does a Gastroenterologist Do?

People often make assumptions about medical specialists and their areas of expertise. This is certainly true with gastroenterology, where many people assume that gastroenterologists are experts in all things related to the digestive tract.

Gastroenterologists are experts in diseases of the digestive tract, not syndromes or symptoms. While Gastroenterologists do primarily pay attention to the digestive tract, there are some surprising gaps in their training on the science of digestion. Gastroenterologists primarily focus on performing colonoscopies and upper endoscopies.

They may also do other imaging work of the GI tract, such as an ultrasound, CT scan,MRI, x-rays, and even “pill cameras.” And they may perform studies that assess the motility of the digestive tract. Therefore, if you go to a gastroenterologist your diagnosis will be based on this testing.

Gastroenterology is primarily a specialty in assessing the structure of the digestive tract. Gastroenterologists are focused on diagnosing ulcers, polyps, cancers, and other physically apparent abnormalities of the digestive tract. Surprisingly, they do not have training in nutrition or most reactions to foods. And though the digestive tract is the single most concentrated area of immune activity, gastroenterologists have no special training in immunology.



What Does an IBS Specialist Do?


There are literally hundreds of different causes of IBS and the digestive problems associated with IBS. An IBS specialist does not have any idea about how they will treat an IBS patient when they first meet that patient. Patients with identical symptoms may have radically different causes for those symptoms. An IBS specialist focuses on the detective work required to develop the proper treatment plan for each unique patient.


This process involves a detailed evaluation of how the body is responding to the foods in the diet (food allergies, intolerances, and sensitivities), and a thorough assessment of the profound ecosystem (including probiotics, yeast, bad bacteria, and parasites) that is contained within the digestive tract. It may also involve evaluating enzyme production, acid production, and the overall functioning of the digestive tract.


IBS specialists do not do what gastroenterologist do, and gastroenterologists do not do what IBS specialists do. These are completely different specialties. There is only a very tiny amount of overlap with regard to stool testing. But even this is extremely minor as the IBS specialist utilizes much more advanced stool analyses.


If you have IBS and continue to see gastroenterologists, then you will continue to get the same kind of testing and treatment that you’ve always received, even if you go to the Mayo Clinic, or the Cleveland Clinic, or any other big name medical facility or highly regarded expert – because they have a “standard of care” that recommends limiting testing. If that hasn’t helped, or you’d simply like to begin your journey with a different approach, then you need to see an IBS specialist. Your experience will be very different, which makes it far more likely that the outcome will be very different.


If you suffer from Irritable Bowel Syndrome, you need an IBS specialist. The link to the article can be found HERE.


My friend Melissa, suggested to me, that it would idea to follow a FODMAP DIET. The article about the Fodmap Diet says,

"The FODMAP theory holds that consuming foods high in FODMAPs results in increased volume of liquid and gas in the small and large intestine, resulting in distention and symptoms such as abdominal pain and gas and bloating. The theory proposes that following a low FODMAP diet should result in a decrease in digestive symptoms. The theory further holds that there is a cumulative effect of these foods on symptoms. In other words, eating foods with varying FODMAP values at the same time will add up, resulting in symptoms that you might not experience if you ate the food in isolation. This might explain the mixed results of studies that have evaluated the effects of fructose and lactose, two types of carbohydrates, on IBS. Ongoing research is being conducted as to the accuracy of the FODMAP theory and the effectiveness of the diet for IBS. Research into its effectiveness for IBS is at a very preliminary stage and it is unknown at this point if following such a diet would be safe for your health over the long term. As with any new treatment or dietary approach, it is always best to discuss the issue with your own personal physician."

Common High FODMAP Foods for IBS:

Fruits:

Apples
Apricots
Cherries
Mango
Pears
Nectarines
Peaches
Pears
Plums and prunes
Watermelon
High concentration of fructose from canned fruit, dried fruit or fruit juice

Grains

Level of FODMAPs is increased when these foods are eaten in large amounts:

Rye
Wheat

Lactose-Containing Foods

Custard
Ice cream
Margarine
Milk (cow, goat, sheep)
Soft cheese, including cottage cheese and ricotta
Yogurt

Legumes

Baked beans
Chickpeas
Lentils
Kidney beans

Sweeteners

Fructose
High fructose corn syrup
Isomalt
Maltitol
Mannitol
Sorbitol
Xylitol

Vegetables

Artichokes
Asparagus
Avocado
Beets
Broccoli
Brussel sprouts
Cabbage
Cauliflower
Garlic (with large consumption)
Fennel
Leeks
Mushrooms
Okra
Onions
Peas
Radiccio lettuce
Scallions (white parts)
Shallots
Sugar snap peas
Snow peas

Common Low FODMAP Foods

Fruits

Banana
Blueberry
Grapefruit
Grapes
Honeydew melon
Kiwi
Lemon
Lime
Mandarine oranges
Orange
Raspberry
Strawberry

Sweeteners

Artificial sweeteners that do not end in -ol
Glucose
Maple syrup
Sugar (sucrose)

Lactose Alternatives

Butter
Hard cheese, brie and camembert
Lactose-free products, such as lactose-free ice cream and yogurt
Gelato
Rice milk
Sorbet

Vegetables

Bell peppers
Bok choy
Carrots
Celery
Corn
Eggplant
Green beans
Lettuce
Parsnip
Scallions (green parts only)
Sweet potato
Tomato

Grains

Oats
Gluten-free products
Spelt products



Now I want to get into SIBO. If you have Gastroparesis, SIBO is a legit concern. Crystal Saltrelli wrote an article about SIBO not too long ago. Here is an exert of her article about SIBO if you would like to read it,

"What is SIBO? SIBO stands for small intestinal bacterial overgrowth. It’s also sometimes called small bowel bacterial overgrowth or SIBO. It all means the same thing: there are bacteria in your small intestine that are not supposed to be there. What causes SIBO? One of the biggest risk factors for SIBO is… slow gut motility. Muscular contractions within the gut are supposed to sweep things, both food and bacteria, through the GI tract. When it doesn’t, bacteria can take hold and multiply in places where they don’t belong. This is bad news for GPers, of course, and even worse if you’re chronically constipated, as bacteria may migrate upward from the colon to the small intestine, as well. What’s more, it’s thought that protein pump inhibitors (PPIs), which many GPers are immediately prescribed, may encourage the growth of bacteria by limiting (or even eliminating) the anti-bacterial effects of acid in the stomach."

You can find Crystal's Article by clicking HERE.




The link to the article can be found >HERE.

Mayo Clinic - Day Five. Follow up Visit with the Doctor

I met with the doctor today at Mayo to go over all of my test results from this week of testing.

We started off talking about my lab work. My labs were normal, except for my enzymes. The number was 108 and normal is around 40. That kind of bothers me because my liver enzymes were also really high in the hospital, in the 440s to 500s. He is going to recheck my labs in three months to rule out chronic liver disease, which sounds a bit scary. My white blood cell count was up, at 12.8. I don't have any explanation for that except for the throat infection I vomited myself into last week.

My 48 hour BRAVO TEST was positive. The test came back showing three different occasions for heartburn. The regurgitation I had did not correspond with reflux events on the Bravo meter device.

I want to address the heartburn thing. I know what heartburn feels like and I swear that I did NOT feel the heartburn while doing the Bravo test. I have been vomiting up stomach acid, but I thought that was because there was nothing left on my stomach. Am I just so used to the acid reflux that I can't tell when it's occurring now?

My esophagus looked normal and there wasn't any damage. I'm not sure how that happened because it was so swollen and sore last week. I still have issues swallowing and I have the bravo capsule attached to my esophagus until it falls off.

I have to manage this like GERD. I've tried Protonix, Pepcid, Prevacid, Prilosec, and Dexilant in the past to control acid reflux. So, the doctor called in some ACIPHEX to help control my symptoms. He told me to try this for three months. He also told me to learn DIAPHRAGMATIC DEEP BREATHING. Dr. Bouras said that will help me to help control the vomiting. I have to come back to the Mayo Clinic to meet with behavioral specialists to learn how to this technique but it will have to be approved by my insurance before I can schedule the appointment. But, the deep breathing will help me hold the food down.

If the medication does NOT work, then he will have to do surgery. He recommended a NISSEN FUNDOPLICATION.

The doctor also cleared me to start back on BENTYL. This is great news because my stomach spasms hurt SO much! This will help them subside. He did caution me to be careful about these types of medication because they can make gastric emptying even slower.

If I'm still having issues three months from now on the new PPI and with the deep breathing, he also mentioned doing a Sleuth Study which is a reflux study that isn't just about acid, but any kind of reflux. I'm sorry that I don't have a link for you but I can't find anything on the Internet about it. He also mentioned the Nissen, as I mentioned before. That would make it impossible for me to vomit and could create issues for me swallowing.

I also have severe constipation. Nothing goes down and everything comes back up so he suggested Milk of Magnesium at night. I've been doing that but I guess I'll up the dosage. He said that in some cases, severe constipation can lead to upper GI motility issues. I'm to take 2 - 4 tablespoons of Magnesium at bedtime and avoid any medications that could cause constipation.

He may eventually do rectal testing on me. Man, that sounds like fun! Kidding. Anyway, he said that even though your colon could be normal (mine was via a colonoscopy) that you can still have rectal issues. There are tests to see if the muscles are functioning properly and he would also check for any possible blockages. He also mentioned doing another test called the PELVIC FLOOR TEST. I had never heard of such a thing. It's a group of muscles that control your bladder and bowel movements and this test makes sure that group of muscles work properly.

I asked him if there was anything else I could take for the nausea because the Zofran is hit or miss and Phenergan, well, doesn't last that long. I think I'm building up a tolerance. he said that I could take SCOPOLAMINE patches, which you put behind your ear and wear for three days but they have the potential to make you sleepy. So, I'll ask my doctor about those when I get home. I am going to straight up ask for pain patches too until the spasms are under control.

So, I still have motility issues. I'm meeting with a new PCP this week as well so that I can actually get more refills on Phenergan (more than 2 refills at a time), ask about the patch, and talk to him about everything that's been going on. I know he can't help with GP or motility issues, but he can help me with the stress and coping with such things. I had been seeing another doctor as my PCP but he's been at the practice less and less, having his PA's cover it instead and some of them really aren't that bright. If I am paying for a visit and I haven't slept in three days because of vomiting - don't turn me away with a prescription for 12 phenergan tablets and a pat on the head. That was the last straw for me, I think. I'm in the process of getting ALL of my medical records together for the new doctor. He might be a bit overwhelmed. My file looks like 100 Stephen King novels packed into one.

TRDL; my liver enzymes are high and need to be tested in three months to rule out chronic liver disease. Severe acid reflux is causing me to keep vomiting everything up. The doctor gave me medicine and if it doesn't work, along with deep breathing, I will need to have a stomach operation wherein, basically, they wrap my stomach around itself as well as other testing.