Quantitative analysis of swallowing in Parkinson ’ s disease before and after riboflavin

Purpose: to verify the quantitative changes in the swallowing dynamics in patients with Parkinson ́s disease submitted to treatment with riboflavin, red meat and poultry removed during one year period. Methods: sixteen patients with Parkinson ́s disease participated in the study; the mean age was 67.25 years, the mean degree of disease severity was II to III, and the mean time since the diagnosis of the disease was 3.5 years. Videofluoroscopic evaluations were performed before and one year after treatment with riboflavin and diet with restriction of read meat and poultry. Analyzed were: presence of complaints related to swallowing and quantitative analyses of swallowing includind computerized measurements of hyoid bone and cricoid cartilage displacement, opening of the superior esophageal sphincter and pharyngeal constriction. Results: decrease of complaints was observed after administration of riboflavin. About the quantitative measures after riboflavin, there were a increase in the opening of the superior esophageal sphincter for all consistencies offered, an increase in the pharyngeal constriction for the thickened liquid, a reduction in the hyoide bone displacement, and an increase or a reduction in the cricoid cartilage displacement for each consistency, with significant reduction for the liquid. Conclusion: quantitative measurements made in the movement of organs associated with swallowing showed no significant differences between pre-and post-riboflavin, and red meat and poultry removed.

submitted to riboflavin intake and restriction of red meat and poultry for one year.

METHODS
This research was approved by the Federal University of São Paulo State/São Paulo Hospital Comitê de Ética em Pesquisa (Research Ethics Committee), Protocol 0360/06.
Sixteen PD patients participated in this study (8 men and 8 women), at an average age of 67.25 years, an average severity level of the disease from II to III according to the Adapted Hoehn & Yahr Scale 11 and the average PD diagnosis time of 3.5 years.At the beginning of the study, 14 patients had already been taking PD medication, and this was not interrupted for the study.No patient underwent speech therapy during the study period.After videodeglutogram were performed orientations when necessary, regarding food consistency and forms of offer.
not only represents a specific alteration of a certain ethnic group 5 .
Swallowing disorders in Parkinsonism may be present at different levels, affecting oral, pharyngeal and esophageal phases 6 .Studies 7,8 report that patients with PD often develop dysphagia in the course of their disease, having difficulties to start swallowing and occasionally pulmonary aspiration of liquids, what impairs the individuals' clinical, nutritional and hydration state and leads to complications such as malnutrition and aspiration pneumonia.Studies in the Parkinson's literature report that pneumonia is the most common cause of deaths among patients with PD 9,10 .
About the motor gain presented by patients with PD submitted to the administration of riboflavin and restriction of red meat and poultry 3 , began this research to determine whether these gains could also be applied to swallowing, as there are changes in the dynamics of swallowing in PD The purpose of this study was to analyze quantitative changes in the swallowing dynamics in patients with Parkinson's disease, who were • maximum displacement of the cricoid cartilage: tracing of resting-state images, as well as the moment of higher elevation of the hyoid/laryngeal complex, were made.Initially, two tangent lines were traced, one to the free border level of the vocal folds, and the other to the anterior wall of the trachea, a little below the larynx.The crossing of these two tangent lines with two other fixed lines was selected, thus comprising a 90° right angle in one of the cervical vertebrae, copying this selected image.Thereupon, the same procedure of tangent lines was carried out on the free border of the vocal folds and the trachea of the 90° angle, on the same vertebra used on the resting state, on the image of higher larynx elevation.At that moment, the selected resting--state image was overlapped, thus allowing the cricoid cartilage displacement to be measured; • maximum pharyngeal constriction: measurement made between the difference of both pharynx in resting state and its area occupied either by air or food residues at the moment of pharynx higher constriction during swallowing.The tracing of the resting-state image started in the anterior tubercle of the atlas vertebra, following inferiorly towards the arytenoid cartilage and the upper part of the vocal folds.It followed superiorly, outlining the epiglottis, the base of tongue and the velum until it reached the posterior nasal spine of the horizontal plate of the palatine bone.As for the image for higher pharyngeal constriction, either the food residue area or the remaining air space was outlined; • maximum pharyngoesophageal transition (PET): maximum opening for food passage during swallowing.For this measurement to be made, we chose the moment of higher opening of sphincter, in a 1-cm region below the level of the vocal folds, thus taking opening measurement by tracing a horizontal line in the extension of the entire food bolus column.Measurement of the upper esophageal sphincter was considered null in the resting state.The authors understand by the terminology of functionality in the swallow, the occurrence of this function safely and effectively, without risking the protection of the lower airways, and at a time able to keep the nutritional aspects appropriately.
In order to analyze the results, significance (p) level of 5% (0,05) was adopted.Statistical significances is marked with an asterisk (*).
The patients were referred to the doctor in charge of riboflavin administration before the beginning of this treatment.According to the doctor, each patient received 30 mg every eight hours, totaling 90 mg of riboflavin daily.Red meat and poultry restriction was mandatory during the study, and the patient was advised by the medical team to replace that diet with other protein sources.It is worth mentioning that, every three months, each patient's serum ferritin was analyzed by the medical team, so that it was possible to confirm that their iron reserves were within normal limits.
The patient was initially asked whether they had any swallowing-related complaints.Later on, the target swallowing study was conducted by means of the videofluoroscopic swallowing study (VFSS), following the Federal University of São Paulo State -Medicine School of São Paulo protocol 12 .During the study, the patient was kept in a osthostatic, lateral and front positions.The test was carried out with the EDR-750B X-ray device, and the videos were recorded with an X690 Semp camcorder.In the analysis of this study, the following offers were considered: 5 ml of a thin liquid (water + barium) offered in a syringe; 5 ml of a thick liquid (pure barium) offered in a syringe; 5 ml of a semi-solid mixture (yogurt-like sweet fromage frais + barium) offered with a spoon; and a solid mixture (a small piece of cheese bread + barium).
A year after riboflavin intake, the patients were recalled and again submitted to the whole procedure above described, so that it was possible to analyze the development of the swallowing dynamics process.
In the analysis of the VFSS, swallowing-related structures were measured by means of an image processing program, the ImageJ 13 , developed by the National Institute of Health.For such analysis, appropriate lateral view images for each measurement were selected and digitalized.For program calibration, in order to get information on the distance or area selected in centimeters in each image, a metal marker was used -placed in the mastoid region -, thus allowing to provide the program with its diameter value.The measurements taken were: • maximum displacement of the hyoid bone -image tracings were made on the resting--state images and at the moment of maximum excursion of the hyoid/laryngeal complex during swallowing.Initially, the intersection between a tangent line to the anterior portion of the hyoid bone and another tangent line to the inferior margin was considered.Next, a right angle was traced -always considering the same individual's cervical vertebrae.At a later time, swallowing, since he PET opening is strictly related to the hyo-laryngeal complex raise, such as a lever system, and to the food bolus volume and consistency as well.
Variations in the maximum pharyngeal constriction percentage (Table 3) did not obtain statistical significance, and showed both values lower than or greater constriction, depend of the food consistency analyzed, when comparing the two moments.
The maximum displacement of the hyoid bone (Table 3) were difficult to read, due to the variety of its movement standards.A slight reduction in its displacement values was observed, with no interference in swallowing functional aspects.

RESULTS
Sixteen patients participated in this study.However, due to the image quality of the VFSS which, at times, did not allow for reliable assessment of the results, a lower N occurs in some tables.
It is possible to observe in Table 2 the percentage of complaints in PD patients in the pre and post riboflavin moments.The analysis of the complaint was made by its presence or absence.The authors did not relate the specificity of complaints.
The maximum PET opening showed variations in comparing the two moments, with no statistical significance, with a slight increase at the post taking moment (Table 3) for all the consistencies analyzed.This comparison might suggest a more efficient  range, but this comparison may be questioned by the difference in the volume offered.Data found were similar for all the study patients, even those that did not engage in using the medication for PD.Analyzing the tests in a qualitative way, according to the clinical practice of the authors, the swallowing of the patients in study were classified as normal both times.This finding suggests that the patients in this study did not show changes that could compromise the safety and efficacy of swallowing.
The cricoid cartilage displacement (Table 3) shows sometimes a slight increase of the displacement index, sometimes slight reduction.To the thin liquid consistency, a significant reduction in this displacement was found, although interference in swallowing functional aspects was not observed.
Table 4 shows the comparison of the data found in maximum opening of PET and displacement of the hyoid bone in this study, with data of normal literature 14 .Can be verify that the data of the patients in this study are higher compared with the normal

DISCUSSION
Prevalence of dysphagia in PD demonstrates the need for speech therapy activity in these patients, and the understanding by this professional regarding the pharmacological interference in the pathophysiology of swallowing.According to the literature 7,8 , the presence of dysphagia in PD is common, especially with the progression of disease, leading to clinical disorders, including the occurrence of malnutrition, dehydration and aspiration pneumonia, due to changes in swallowing function .According pesquisa 15 performed, the average lifespan of PD patients after the onset of symptoms of dysphagia shall be 24 months.
As some studies report in the literature 16,17 the swallowing-related complaints in patients with PD may not frequently be correlated with the process itself.The decrease of the complaints in this study in the post-riboflavin may suggest optimizing in the patients perceptions of symptoms presented, which does not indicate an improvement in the function itself.
Authors 18 observed higher UES opening when more dense pure barium was swallowed than when less dense pure barium was swallowed.In another study 19 the authors suggest to use thickened liquid in order to reduce tracheal aspiration of thin liquid.
In a research 20 the authors conclude that swallowing thickened liquid is safer than swallowing thin liquid for patients with PD.It was observed at VFSS of patients who participated in this study that this consistency presented more representative food stasis than the others, which might explain the fact that pharyngeal constriction occurs at a higher proportion in this consistency, aiming at inducing higher pressure for food bolus to go down.
In the literature, the analysis of the hyoid bone displacement is divided into anterior displacement and vertical displacement.Therefore, it makes comparison of data in this study difficult.In the studies, some authors 21 state that the anterior displacement of the hyoid bone is more variable, whereas another authors 22 report that the anterior displacement of the hyoid bone is less variable, as well as larger when compared with its vertical displacement.They also state that the amplitude of the vertical displacement of the hyoid bone varies according to food consistency.
The differences found before and after taking riboflavin, even though some differences had statistical significance, did not influence those patients' swallowing functional aspects, given that, a year after the study was conducted, those patients' swallowing was safe and efficient.In the study group, there was no influence on swallowing pattern displayed by patients with the use of riboflavin and restriction of red meat and poultry.It is believed that if the analysis performed in this study occurred in patients with PD who presented swallowing disorders more apparent, the results could be different.Thus, it is suggested to continuing studies of quantitative measurement in PD patients subjected to this intervention.

CONCLUSION
In conclusion, quantitative measurements made in the movement of organs associated with swallowing showed no significant differences between pre-and post-riboflavin, and red meat and poultry removed.medidas, impedindo uma comparação entre esses dados.A Tabela 4 demonstra a comparação de duas variáveis do estudo (abertura da TFE e deslocamento do osso hioide) com dado de literatura 14 .
Compared to the data in the literature 14,[23][24][25][26][27][28][29] the measurement values of the hyoid bone displacement, maximum pharyngeal constriction and maximum UES opening were found to be higher, even when compared to nondysphagic individuals.Such a fact may result from different methods to take measurements, thus preventing a comparison of these data.Table 4 shows the comparison of two variables in the study (PET opening and displacement of the hyoid bone) with data of literature 14 .
From a study in which higher hyoid bone displacement values for nondysphagic elderly people in comparison to young people were found, the authors 30 conclude that this deviation may be a result from a lower position of the larynx in elder people's necks.

Table 2 -Numerical and percentage distribution of patients according to the presence or absence of complaints related to swallowing, in the pre-and post-riboflavin (p=0,257).
Legend: N= number of patients; %= percentage.

Table 3 -Numerical distribution, mean and standard deviation of the variable maximum PET, maximum pharyngeal constriction, maximum displacement of the hyoid bone and maximum displacement of the cricoid cartilage, in centimeters, for consistencies thin liquid, thick liquid, pasty and solid in pre and post-administration of riboflavin. Consistency Maximum PET Pharyngeal constriction Hyoid bone displacement Cricoid cartilage displacement
Legend:= mean; N= number of patients; SD= standard deviation; p= significance; PET= pharyngoesophageal transition; L= thin liquid; TL= thick liquid; P= pasty; S= solid.

Table 4 -Comparison of the numerical distribution, mean and standard deviation of the variable maximum PET and maximum displacement of the hyoid bone in centimeters for thin liquid consistency, in the pre-and post-administration of riboflavin, with data from the literature 14 Consistencies Volume (milliliters) PET Hyoid bone displacement
Legend:= mean; N= number of patients; SD= standard deviation; p= significance; PET= pharyngoesophageal transition; L= thin liquid.