Intratympanic Dexamethazone versus High Dosage of Betahistine in the Treatment of Intractable Unilateral Meniere Disease Silviu Albu, Felician Chirtes, Veronica Trombitas, Alina Nagy, Luigi Marceanu, Gregorio Babighian, Franco Trabalzini PII: DOI: Reference:

S0196-0709(14)00262-2 doi: 10.1016/j.amjoto.2014.10.032 YAJOT 1487

To appear in:

American Journal of Otolaryngology–Head and Neck Medicine and Surgery

Received date: Revised date: Accepted date:

7 July 2014 21 October 2014 25 October 2014

Please cite this article as: Albu Silviu, Chirtes Felician, Trombitas Veronica, Nagy Alina, Marceanu Luigi, Babighian Gregorio, Trabalzini Franco, Intratympanic Dexamethazone versus High Dosage of Betahistine in the Treatment of Intractable Unilateral Meniere Disease, American Journal of Otolaryngology–Head and Neck Medicine and Surgery (2014), doi: 10.1016/j.amjoto.2014.10.032

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ACCEPTED MANUSCRIPT Intratympanic Dexamethazone versus High Dosage of Betahistine in the Treatment of Intractable Unilateral Meniere Disease. , Felician Chirtes 1, Veronica Trombitas 1, Alina Nagy 2, Luigi Marceanu 3,

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Silviu Albu

Gregorio Babighian 4 and Franco Trabalzini 4

Second Department of Otolaryngology, Iuliu Hatieganu University of Medicine and Pharmacy

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1

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Cluj-Napoca, Cluj-Napoca, Romania. Ro-Neuro Clinic Cluj-Napoca, Romania

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University of Medicine and Pharmacy Brasov, Romania.

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Operative Unit of Otolaryngology and Otosurgery, Padua University, Padua, Italy

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Silviu Albu, MD

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Corresponding author:

Professor, II-nd Department of Otolaryngology, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Str. Republicii nr. 18, 400015 Cluj-Napoca, Romania. Fax: 0040 264 598278, E-mail: [email protected]

Sponsorship: no funding was received for this study Conflict of interest: nothing to declare

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ACCEPTED MANUSCRIPT Abstract. Purpose. The objective of our randomized, double-blind study was to compare the effectiveness

patients with intractable unilateral Meniere disease (MD).

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of intratympanic (IT) dexamethasone versus high-dosage of betahistine in the treatment of

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Materials and Methods. Sixty six patients with definite unilateral MD were randomly divided

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in two groups: Group A received a combination of IT dexamethasone (DX) and identicalappearing placebo pills while Group B received a combination of high-dosage betahistine and IT

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saline. Intratympanic injections were repeated for three times with an interlude of 3 days. Highdosage of betahistine entailed in 144mg/day. Mean outcome measures consisted in vertigo

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control, pure tone average (PTA), speech discrimination score, Functional Level Score,

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Dizziness Handicap Inventory and Tinnitus Handicap Inventory. Results. Fifty nine patients completed the study and were available at 12 months for analysis. In

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Group A complete vertigo control (class A) was attained in 14 patients (46.6%) and substantial

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control (class B) in 7 patients (20%). In Group B, 12 patients (41%) achieved complete vertigo control (class A), 5 patients (17%) substantial control (class B). There is no statistical difference in vertigo control between the two treatment groups. In Group A hearing was unchanged in 14 patients and improved in 4 patients, while in Group B hearing was unchanged in 16 patients and improved in 2 patients. Conclusions. Our preliminary results demonstrate that high-dosage of betahistine achieved similar outcomes as IT dexamethasone in the control of vertigo and hearing preservation. Key words: Meniere disease, intratympanic dexamethasone, high-dosage of betahistine, vertigo control. 2

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Meniere’s disease (MD) represents the second most frequently encountered 1, 2

. Management is aimed in decreasing the

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causes of peripheral vertigo in clinical practice

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Introduction.

frequency of vertigo spells, reducing tinnitus, and preserving or even improving of hearing 3.

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Various treatments are prescribed in a step-wise approach ranging from low-salt diet, diuretics, betahistine, to intratympanic injection of gentamicin or corticosteroids and even surgery 3. The

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management is even more intricate since a complete or partial resolution of vertigo spells could

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be attained spontaneously after 7 - 10 years from identification of MD

4-6

. Betahistine has been

extensively used in the treatment of MD with disagreeing results reported

7, 8

. Nevertheless,

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recently, an open trial demonstrated that higher-dosage of betahistine (144mg/day) are able to significantly reduce the number of vertigo attacks in MD 9. On the other hand, lately the use of

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intratympanic (IT) corticosteroids became popular

3, 10

. Their usage is grounded on the concept

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of an immune-mediated pathology in the development of MD 1, 2, 11. It was demonstrated that IT injected corticosteroids attain higher inner ear concentrations than those obtained through

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systemic administration

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. Quite a lot of papers have been published on the use of IT

corticosteroids in MD with conflicting results and no consensus on the protocol of IT administration has been reached 13-19. The goal of the present paper was to compare the effectiveness of IT dexamethasone versus high-dosage of betahistine in the treatment of patients with MD.

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Material and Methods. This study was approved by the Institutional Review Board of the two

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medical centers (Azienda Ospedaliera-Università of Padova, Italy, and Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca) in accordance with the Guidelines for

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Protection of Human Subjects. All patients were provided with thorough explanations about the risks and benefits associated with the procedures and signed an informed consent form before

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entering the study. Included in the study were adult patients with unilateral definite MD fulfilling

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the criteria of the American Academy of Otolaryngology–Head and Neck Surgery (AAOHNS)20. All of these subjects failed a trial of 6 months of low-salt diet and diuretics. Excluded

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were patients presenting: a) other peripheral or central vestibular disorders; b) noise-induced hearing loss; c) middle ear diseases; d) previously treatment with IT gentamicin or

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corticosteroids or previous ablative ear surgery for MD; e) bilateral MD; f) allergy to betahistine;

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g) simultaneous treatment with diuretics, corticosteroids and vasodilators 9, 21. Patients underwent a complete otoneurological examination, and auditory testing consisting in

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pure tone audiometry (PTA) with 4 frequency average (0.5, 1, 2, and 3 kHz) and speech discrimination score (SDS). Magnetic resonance imaging was obtained in order to rule out a cerebello-pontine pathology. The Functional Level Score (FLS), Class and vertigo control were computed according to the 1995 AAO-HNS guidelines

20

. According to the same guidelines, a

change of 10 dB or more in PTA or a change of 15% in SDS were considered clinically significant. The Dizziness Handicap Inventory was evaluated for every patient

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. It contains 25 questions

divided into physical, emotional, and functional subgroups. Each question was responded with “no” (assigned 0 points), “sometimes” (assigned 2 points), or “yes” (assigned 4 points). The total 4

ACCEPTED MANUSCRIPT score ranges from zero (no incapacity) to 100 (severe incapacity). For tinnitus we used the Tinnitus Handicap Inventory (THI), completed in each patient. THI is a 25-item questionnaire 23

. Each point was answered with “yes”

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designed to assess the harshness of tinnitus frustration

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giving 4 points, “sometimes” giving 2 points, and “no” 0 points. The lower the total score, the

treatment and at the end of the follow-up period.

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less was the tinnitus handicap. All of these parameters were obtained before the beginning of the

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Patients were randomly divided in two groups, each comprising 33 patients. Randomization was performed with a computer-generated number sequence of 0 (Group A) and 1 (Group B) number

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sets indicating whether the patient was allocated to Group A or B. Randomization was achieved by one investigator only (FC) one day before the injection procedure. Both the surgeons (SA, GB

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and FT) and the patients were blinded to the treatment. Group A received a combination of IT

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dexamethasone (DX) and identical-appearing placebo pills while Group B received a combination of high-dosage betahistine and IT saline. Dexamethasone and saline were injected

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following the well-known procedure: in the supine position, the patient turned the head 45°

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toward the unaffected ear. Following anesthesia of the eardrum, using a 22-gauge spinal needle, 1mL of dexamethasone (4mg/mL) or saline were injected through the tympanic membrane into the middle ear. Patients kept the supine position with the injected ear facing upward for 30 minutes refraining from swallowing or talking. The injection was repeated for three times with an interlude of 3 days (3 injections every 3 days). High-dosage of betahistine consisted in 144mg/day (48 mg tid) 9. Audiometric testing and completion of questionnaires were performed by different researchers (FC, VT, LM, AN) blinded to the surgeons. During the study period, at two months interval all the patients were surveyed in the clinic. Compliance to treatment was checked through telephone

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ACCEPTED MANUSCRIPT calls by the clinical investigators. On the other hand, at every interim visit, the patient had to return the empty medication packages. Side-effects of the treatment were recorded in each

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patient.

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Another aim of the study was to compare the promptness of vertigo fading in the two treatment

months and then every 3 months for up to 1 year.

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arms. Therefore, the mean number of vertigo spells per month was recorded at baseline, at 1, 3

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Sample size was designed with the software available from DSS Research Tools (http:// www.dssresearch.com/toolkit.). Sample size was calculated to detect differences of 15% in the

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probability of primary endpoint (the probability of success for Group A was assumed to be 85%, whereas within the Group B, it was assumed to be 70%) with a Type I error of 5% and a statistic

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power of 80%. For each group, 27 subjects were required. In order to compensate for potential

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drop-outs, 33 patients were enrolled in each study arm.

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Statistical analysis was performed using SPSS ver. 20.0 (SPSS Inc, Chicago, IL). The Student ttest was used to detect significant differences between groups, after a Kolmogorov–Smiranov

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(K-S) test for normality. Differences between categorical variables were assessed using the chi square test. Data were expressed as mean ± standard deviation (SD). A p value of less than 0.05 was considered significant.

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ACCEPTED MANUSCRIPT Results. Between January 2007 and January 2012, 66 patients with unilateral definite MD presenting at the two mentioned Departments met the inclusion criteria and were included in the

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study. The mean age was 50.2 years (SD ± 14.3 years) in Group A, and mean age was 51.5 years

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(SD ± 14.3 years) in Group B. The baseline demographic and functional characteristics distributions among the two groups are presented in Table 1. No statistically significant

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difference was observed between all the above parameters among the two groups. One can see

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that no MD patients with stage 1 and/or FLS below 3 are included in the present study. This is to

excluded from the present analysis.

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certify that patients with possible and probable MD, with mild vestibular dysfunction were

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Fifty nine patients completed the study and were available at 12 months for analysis, while 7 patients (3 in Group A and 4 in Group B) were excluded because of insufficient compliance.

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Vertigo control reported according to the 1995 AAO-HNS guidelines in the two treatment

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groups is presented in Table 2. At 1 year follow-up, in Group A complete vertigo control (class A) was attained in 14 patients (46.6%) and substantial control (class B) in 7 patients (20%). In

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spite of 1 or 2 IT retreatments, eight patients reported limited control (class C and D) and one patient had no control of vertigo (class E). In Group B, 12 patients (41%) achieved complete vertigo control (class A), 5 patients (17%) substantial control (class B) and 10 patients had limited control (class C and D), while failure was reported in 2 cases (class E). Failures in both treatment groups were scheduled for IT gentamicin. As one can see form Table 2 there is no statistical difference in vertigo control between the two treatment groups. At 12 months followup, level one of FLS was attained in 14 patients and level 2 in 9 cases in Group A, while in Group B 10 patients attained level one and 9 patients level 2. There is no significant difference between the two groups. 7

ACCEPTED MANUSCRIPT The mean number of vertigo attacks per month at baseline and during the follow-up is represented in Figure 1. The overall number of vertigo spells per month at baseline was 8.6 in

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Group A and 7.9 in Group B. The follow-up evaluation showed a significant reduction of the

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mean number of attacks per month in both groups: 1.8 in Group A versus 4.3 in Group B at 1 month, 1.5 in Group A versus 2.4 in Group B after 3 months from the start of treatment.

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However, we realized that intratympanic dexamethasone has an immediate effect versus

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betahistine for which the same expected effect is to be observed after 3 months. Hearing outcomes following treatment are presented in Table 3. The mean PTA pretreatment

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were 57.4 (SD, 14.7) for Group A and 58.2 (SD, 13.9) for Group B. After 12 months of therapy the PTA values were 55.8 (SD, 15.5) for Group A and 56.1 (SD, 12.5) for Group B. Generally,

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post-therapy there were no statistically significant variations within and between the two groups.

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Following therapy, there were also no significant fluctuations in SDS in both groups. According to the 1995 AAO-HNS criteria, in Group A hearing was unchanged in 14 patients, improved in 4

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patients and worsened in 12 patients. According to the same criteria, in Group B hearing was

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unchanged in 16 patients, improved in 2 patients and declined in 11 patients. Following therapy, the perceived dizziness handicap assessed by DHI displayed a significant reduction in both groups. However, the difference between treatment groups was not significant. A significant reduction in tinnitus annoyance assessed by THI at the end of the follow-up was reported in both treatment groups. The difference among the two groups was not significant. High-dosage of betahistine did not cause significant side effects. Side effects recorded in Group B were stomach fullness in 4 cases, diarrhea in 3 cases, nausea in 4 cases, headache in 7 patients and mild vegetative symptoms in 6 patients. However, these side effects did not cause an interruption of the therapy. We encountered three ear drum perforations healed spontaneously. 8

ACCEPTED MANUSCRIPT Discussion. Betahistine is a H1-agonist and H3-antagonist betahistine increases the blood flow within the inner ear

9, 25

9, 24

. In animal experiments

. A better inner ear perfusion would

9, 24, 25

. In animal experiments the betahistine

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production and re-absorption of endolymph

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hypothetically decrease the endolymphatic pressure by attainment of a steadiness between

outcome turned to be concentration-dependent: an increased concentration was related with an 24

. In agreement with these experiments, Strupp et al.

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improved inner ear blood flow

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recently

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demonstrated in a clinical trial the dose-dependent action of betahistine. These authors have clearly demonstrated that in the long-term, in contrast with low dosage, high dosage of

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betahistine is able to significantly diminish the number of vertigo spells in MD patients. 1, 2

. Thus, the

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Different studies have pointed out that MD is an immune mediated disease

beneficial properties of IT steroids could be owed to their anti-inflammatory and

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immunosuppressive effects. In addition, steroids are able to adjust ion and fluid inner ear

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homeostasis through alterations in potassium transport, induction of mineralcorticoid receptormediated genes and regulation of the aquaporines

11, 26

. In clinical practice, two IT

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corticosteroids have been used: methylprednisolone (MP) and dexamethasone (DX). Pharmacokinetic studies have demonstrated that MP has higher round window permeability and the highest inner ear concentrations were reached after IT of MP

12

. However, diffusion of DX

into the stria vascularis and surrounding tissues was quicker than MP and DX is better tolerated as compared to MP 12, 27. These are the reasons why, in agreement with previous studies 13-19, DX was selected for IT delivery in our study. Different articles have assessed the efficiency of IT DX, with a wide range of results concerning vertigo control: Itoh et al 13, 78%; Hirvonen et al 27, 76%; Barrs et al 17, 60%; Barrs et al, 18 47%; Sennaroglu et al 28, 72%; Dodson et al 10, 54%, Casani et al 29, 43% and Boleas-Aguirre et al 19, 9

ACCEPTED MANUSCRIPT 70%. Generally speaking, these results show the lower efficiency of IT DX to achieve complete vertigo control. As pointed out by Casani et al 29, reduced vertigo control rate could be linked to

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a lower dosage of DX (4 mg/mL), since studies employing higher dosage of DX (16 mg/mL) or

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the usage of DX constant delivery may afford better outcomes. In accordance with the results

46.6% and class B in 20% of patients (see Table 2).

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reported in the literature, in our patient population following IT DX class A was attained in

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Our study is the first one to compare IT DX and high dosage of betahistine in reducing vertigo spells in MD. Vertigo is a subjective measure and thus is prone to be affected by placebo-effects

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and volunteer bias. Through the use of a standardized and blinded setup of the study we tried to circumvent expectation biases and placebo-related biases. The latter effects are likely to favor the

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group having more active interventions and more contacts with health personal. Therefore, IT

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treatments were included in both groups. No significant difference was attained in vertigo control between the two treatment arms. We demonstrated that oral treatment has the same success rate

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as IT corticoid, and thus the drawbacks associated with IT treatment can be circumvented:

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surgical setup with associated costs and patient-related distress, surgery-related complications such as tympanic membrane perforations. Nevertheless, as expected, we have demonstrated that IT dexamethasone has an immediate effect while betahistine is able to afford the same outcome only after 3 months of treatment. Taking into account the speediness of vertigo waning, there is significant reason for the recommendation of the use of IT corticoid in the management of disabling vertigo spells in patients with intractable unilateral Meniere disease. With reference to hearing outcomes, as previously reported, we demonstrated in both treatment groups hearing conservation only in patients reporting good vertigo control. As stated by Casani et al 29, hearing loss is associated with the evolution of MD.

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ACCEPTED MANUSCRIPT Several limitations are however associated with our study: the absence of a placebo-only group limits our conclusions. Nevertheless, Hu et al

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disputed the importance of placebo treatment in

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MD patients. A larger sample should support these preliminary findings.

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ACCEPTED MANUSCRIPT References 1. Minor LB, Schessel DA, Carey JP. Meniere’s disease. Curr Opin Neurol 2004;/17:/9-16.

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2. Sajjadi H, Paparella MM. Meniere’s disease. Lancet 2008; 372: 406Y14.

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3. Coelho DH, Lalwani AK. Medical management of Meniere’s disease. Laryngoscope. 2008; 118:1099-1108.

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4. Silverstein H, Smouha E, Jones R. Natural history vs. surgery for Meniere disease. Otolaryngol Head Neck Surg. 1989; 100:6-16.

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5. Green JD Jr, Blum DJ, Harner SG. Longitudinal follow-up of patients with Meniere disease. Otolaryngol Head Neck Surg. 1991; 104:783-788.

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6. Quaranta A, Marini F, Sallustio V. Long-term outcome of Meniere disease: endolymphatic mastoid shunt versus natural history. Audiol Neurotol. 1998;3:54-60. 7. Jeck-Thole S, Wagner W (2006) Betahistine: a retrospective synopsis of safety data.

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Drug Saf 29(11):1049–1059.

8. James A, Burton MJ. Betahistine for Meniere’s disease or syndrome. Cochrane Database

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Syst Rev 2001;(1):CD001873.

9. Strupp M, Hupert D, Frenzel C, Wagner J, Hahn A, Jahn K et al. Long-term prophylactic

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treatment of attacks of vertigo in Meniere’s disease—comparison of a high with a low dosage of betahistine in an open trial. Acta Otolaryngol. 2008; 128(5):520–524.

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10. Dodson KM, Woodson E, Sismanis A. Intratympanic steroid perfusion for the treatment of Meniere’s disease: a retrospective study. Ear Nose Throat J. 2004; 83:394-398. 11. Merchant SN, Adams JC, and Nadol JB Jr. Pathophysiology of Meniere ’s syndrome: are symptoms caused by endolymphatic hydrops? Otol Neurotol 2005;/26:/74-81. 12. Parnes LS, Sun AH, Freeman DJ. Corticosteroid pharmacokinetics in the inner ear fluids: an animal study followed by clinical application. Laryngoscope. 1999;109:1-17. 13. Itoh A, Sakata E. Treatment of vestibular disorders. Acta Otolaryngol Suppl. 1991;481:617-623. 14. Shea JJ Jr., Ge X. Dexamethasone perfusion of the labyrinth plus intravenous dexamethasone for Me´nie`re’s disease. Otolaryngol Clin North Am. 1996; 29:353-358. 15. Garduno-Anaya MA, Couthino DT, Hinojosa-Gonzalez R, Pane-Pianese C, RiosCastaneda LC. Dexamethasone inner ear perfusion by intratympanic injection in 12

ACCEPTED MANUSCRIPT unilateral Meniere’s disease: a two-year prospective, placebo-controlled, double blind, randomized trial. Otolaryngol Head Neck Surg. 2005; 133:285-294. 16. Silverstein H, Isaacson JE, Olds MJ, Rowan PT, Rosenberg S. Dexamethasone inner ear

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blind, crossover trial. Am J Otol. 1998; 19:196-201.

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perfusion for the treatment of Meniere’s disease: a prospective, randomized, double-

17. Barrs DM, Keyser JS, Stallworth C, McElveen JT Jr. Intratympanic steroid injections for

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intractable Meniere’s disease. Laryngoscope. 2001; 111:2100-2104. 18. Barrs DM. Intratympanic injections of dexamethasone for long-term control of vertigo.

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Laryngoscope. 2004; 114:1910-1914.

19. Boleas-Aguirre MS, Della Lin FR, Santina CC, Minor LB, Carey JP. Longitudinal results

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with intratympanic dexamethasone in the treatment of Meniere’s disease. Otol Neurotol. 2008;29:33-38.

20. Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of

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therapy in Meniere’s disease. Otolaryngol Head Neck Surg. 1995; 113:181-185. 21. Lezius F, Adrion C, Mansmann U, et al. High-dosage betahistine dihydrochloride

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between 288 and 480 mg/day in patients with severe Menière’s disease: a case series. Eur Arch Otorhinolaryngol 2011; 268:1237-40.

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22. Jacobson GP, Newman CW. The development of the Dizziness Handicap Inventory. Arch Otolaryngol Head Neck Surg 1990; 116:424-7.

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23. Newman CW, Jacobson GP, Spitzer JB. Development of the Tinnitus Handicap Inventory. Arch Otolaryngol Head Neck Surg 1996; 122:143-8. 24. Lacour M, van de Heyning PH, Novotny M, et al. Betahistine in the treatment of Ménière’s disease. Neuropsychiatr Dis Treat 2007; 3:429-40. 25. Ihler F, Bertlich M, Sharaf K, Strieth S, Strupp M, Canis M (2012) Betahistine exerts a dose-dependent effect on cochlear stria vascularis blood flow in Guinea Pigs in vivo. PLoS ONE 7:e39086 26. Fukushima M, Kitahara T, Fuse Y, et al. Changes in aquaporin expression in the inner ear of the rat after i.p. injection of steroids. Acta Otolaryngol Suppl. 2004;553:13-18. 27. Hirvonen TP, Peltomaa M, Ylikoski J. Intratympanic and systemic dexamethasone for Me´nie`re’s disease. ORL J Otorhinolaryngol Relat Spec. 2000;62:117-120.

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ACCEPTED MANUSCRIPT 28. Sennaroglu L, Sennaroglu G, Gursel B. Intratympanic dexamethasone, intratympanic gentamicin, and endolymphatic sac surgery for intractable vertigo in Me´nie`re disease. Otolaryngol Head Neck Surg. 2001; 125:537-543.

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29. Casani AP, Piaggi P, Cerchiai N, et al. Intratympanic treatment of intractable unilateral

Otolaryngol Head Neck Surg. 2012; 146 (3): 430-7.

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Meniere disease: gentamicin or dexamethasone? A randomized controlled trial.

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30. Hu A, Parnes LS. Intratympanic steroids for inner ear disorders: a review. Audiol

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Neurotol. 2009; 14:373-382.

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ACCEPTED MANUSCRIPT Table 1. Distribution of baseline characteristics in the two treatment groups of patients with definite

Group B

N=33

N=33

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Group A

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Gender 10/23

13/20

2

3

4

2

Patients (N)

5

20

FLS

3

4

5

Patients (N)

3

21

8

9

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Stage

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Males/Females

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Menière disease.

3

7

21

3

4

5

14

p value

0.44* 4 5

0.59*

5 4

0.27*

57.4 ± 14.7

58.2 ± 13.9

0.69**

SDS (Mean ± SD)

68.4 ± 20.5

67.7 ± 19.5

0.62**

DHI (Mean ± SD)

53.2 ± 13.4

52.7 ± 12.8

0.58**

THI (Mean ± SD)

28.6 ± 14.3

26.7 ± 13.5

0.76**

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PTA (Mean ± SD)

Group A: IT dexamethasone and placebo pills

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Group B: IT saline and betahistine FLS: functional level score PTA: pure tone audiometry SDS: speech discrimination score DHI: Dizziness Handicap Inventory THI: Tinnitus Handicap Inventory * chi square test ** Student t test

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ACCEPTED MANUSCRIPT Table 2. Distribution of patients with definite MD considering class and functional level at the end of the

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Group B

p value

N=30 (%)

N=29 (%)

chi square test

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Group A

A

14 (46.7%)

B

6 (20%)

C

6 (20%)

D

3 (10%)

E

1 (3.3%)

3 4

12 (41.4%)

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5 (17.2%) 5 (17.2%)

0.86

5 (17.2%) 2 (7%)

14 (46.7%)

10 (34.5%)

9 (30%)

9 (31%)

5 (16.6%)

8 (27.5%)

2 (6.6%)

2 (7%)

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2

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1

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Class

FLS

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follow-up.

0.72

Group A: IT dexamethasone and placebo pills Group B: IT saline and betahistine

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ACCEPTED MANUSCRIPT Table 3.

Group B

N=30

N=29

Before therapy

57.4 ± 14.7

58.2 ± 13.9

After therapy

55.8 ± 15.5

p value

0.57

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Group A

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PTA, SDS, DHI and THI scores compared before and after therapy in the two treatment groups.

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PTA (Mean ± SD)

56.1 ± 12.5

p value student t test

0.69 0.58

SDS (Mean ± SD) 68.4 ± 20.5

67.7 ± 19.5

0.62

After therapy

67.2 ± 19.4

65.8 ± 18.7

0.58

p value

0.72

0.64

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DHI (Mean ± SD)

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Before therapy

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0.61

53.2 ± 13.4

52.7 ± 12.8

0.58

After therapy

40.7 ± 16.5

42.3 ± 18.2

0.55

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Before therapy

THI (Mean ± SD) Before therapy

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After therapy

< 0.001