Tonsillitis diagnosis and treatment

LONG-TERM RESULTS OF LOW DOSE GENTAMICIN IN UNILATERAL MENIERE’S DISEASE.

(KEM HOSPITAL PUNE STUDY  2010 to 2020)

Abstract

Recently, the "low dose" protocol with just one or two injections in total spaced 1 month apart, has become the standard treatment for Menieres Disease with gratifying results.

Chemical perfusion of the inner ear is an increasingly popular treatment for Ménière's disease.

 The author reports on the long-term results of 50 patients treated with gentamicin delivered via a round window . Patients with Ménière's disease underwent intra-cochlear infusion of low  gentamicin  (10 mg/ml)  through round window niche  approache. Vertigo was controlled in 95 per cent, whilst preserving hearing in 90 per cent. Of patients. . Tinnitus and aural fullness remained improved in 85 percent.

 Long-term vertigo control can be achieved using low dose gentamicin, whilst preserving hearing and vestibular function in the majority of patients.. The procedure is not (very) painful a  local  anesthetic is used to numb the ear drum. A drop of phenol on the ear drum is one method. Another is a topical anesthetic such as "Emla" cream. Or 10% xylocaine spray. The drug is injected, through RW niche and  left in the middle ear for 30 minutes while the person is lying quietly, and then an attempt is made to clear it from the middle ear via the ET tube (with swallowing and "popping" the ear)..

Keywords: Ménière's Disease, Gentamicin, glycerol CDP

INTRODUCTION

Ménière's disease is a clinical disorder defined as the idiopathic syndrome of endolymphatic hydrops.¹ It is an obvious finding that the Ménière's patients rated their quality of life (QoL) significantly worse in both the physical and psychosocial dimensions than the normal healthy subjects. Previous studies have shown that vertigo has more impact on the physical aspects, whereas tinnitus and hearing loss seemed to influence the psychosocial and emotional aspects more than the physical aspects.² There is no cure for Ménière's disease and interventions do not eliminate the underlying cause of it.

In recent decades, intratympanic gentamicin administration for treatment of Ménière's disease has gained widespread popularity and has demonstrated its clinical effectiveness in the control of intractable vertigo associated with Ménière's disease in a variety of clinical studies.^3, 4 Different methods of administration with gentamicin include multiple daily dosing, weekly administration for four total treatments, low-dose therapy consisting one to two injections month apart with repeating treatment only for recurrent vertigo symptoms,  Although numerous articles have been published using each of these techniques, to date there is no agreement between the otolaryngologists regarding which technique offers the greatest amount of vertigo control with the lowest rate of complications.⁵ According to the concept of partial vestibular ablation, only reduction in vestibular function may be enough in most patients to control the vestibular symptoms of the disease.⁵ However, a recent meta-analysis have shown that the low-dosage method, in contrast, trends toward worse effective vertigo control than the other methods.³

Newer techniques such as the computerized dynamic posturography (CDP) have facilitate objective evaluation of patients with balance disorders. This technique allows analysis of the information supplied by the three sensory systems (i.e. visual, vestibular and proprioceptive) which contribute to the maintenance of balance. CDP has been shown to be a cost-effective and useful technique for the characterization and monitoring of patients with balance disorders.⁶

Materials and Methods

In a prospective clinical study, 50 patients with unilateral definite Ménière's disease according to the definition of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS)⁸ were included in the study from January 2010 to February 2016. Criteria for offering intratympanic gentamicin as a treatment option included intractable vertigo despite lifestyle modification and drug-therapy (2 g per day sodium diet, diuretics and betahistine) for at least 6 months no symptoms suggestive of auditory or vestibular disease in the contralateral ear, and serviceable hearing in the contralateral ear. No patient had history of previous ear surgery, neurologic disorder or aminoglycoside sensitivity.

 At the beginning of study, after explanation of treatment efficacy and probability of complications including dead ear and balance problems such as “curative vertigo”,⁹ each patient gave written informed consent for treatment with intratympanic gentamicin. Pretreatment evaluation included a complete neuro-otologic evaluation, magnetic resonance imaging (MRI), pure tone average (PTA) measurement and impedance audiometry  SISI score  Tone decay  and Glycerol test were recorded. An arbitrary scoring system (0 = none, 1 = mild, 2 = moderate, 3 = severe) used for aural fullness and tinnitus grading.

Ten minutes before the injection, the tympanic membrane was anesthetized with topical 10% xylocaine spray. During the procedure, each patient lay supine and the tympanic membrane of the involved ear was visualized under the operating microscope with the head turned 45 degree to the opposite side to prevent leakage of the solution through the Eustachian tube and to allow for adequate contact of the drug with round window membrane. The 0.5 ml of the stock buffered  gentamicin solution (10 mg/ml) was drawn into a tuberculin syringe and with a  27-gauge, 1.5" slightly bent  needle was injected posterioinferiorly. After the injection, the patient maintained this head position for at least 45 minutes and was told to avoid swallowing to prevent any opening of the Eustachian tube. Few patients experienced some burning pain lasted seconds and resolved immediately

Patients were asked to consider water precautions for two weeks and return for initial follow-up after four weeks. In this follow-up session, the frequency of vertigo, functional level, aural fullness and tinnitus changes and severity of these symptoms were recorded and audiometry, was repeated. Patients were also asked to return after two months for follow up. 

However in our study, using one-shot low-dosage gentamicin led to complete vertigo cessation  in 95% of the patients In the second follow-up, 75% of our patients reported decrease in both aural fullness and tinnitus. Similar findings regarding fullness have been reported previously,²⁰ but our results about tinnitus decrease were striking. Some investigators have proposed that gentamicin exerts its effects primarily not only on the sensory hair cells but also on the destruction of the dark cells within the labyrinth that are responsible for endolymph production. Thus, the effect of gentamicin should be due to not only destruction of vestibular function but also relieving endolymphatic hydrops.¹⁶

Glycerol Positive test clinically confirms endolymphatic hydrops.Patient will have 30 to 40% good hearing and 80 to 90% vertigo control.A positive test would be contra indicated for Labyrinthectomy. Negative test result is indicative of no post op hearing gain and vertigo control and will be contra indicated  for endolymphatic sac surgery

The advantages of dehydration testing cannot be ignored. Such testing can easily be incorporated into a clinical test battery for the diagnosis of Meniere's disease .

Gentamicin vs. steroids vs. vestibular nerve section

There are some complex judgements that come up when one needs to have "something done" about Meniere's disease. Essentially, it comes down to cost vs. benefit

Method	Hearing Risk	Effectiveness	Durability	Other considerations
Steroid injection	Minimal	Moderate	3 months	Not a logical treatment as doesn't last.
Low dose Gentamicin	Minimal	High	Moderate (1-2 yr)	Best choice
High dose gentamicin	Moderate	High	Usually permanent	Permanent imbalance not unusual
Labyrinthectomy	sure loss	High	Permanent	Permanent imbalance AND hearing loss AND highly invasive
Vestibular nerve section	Moderate	High	Permanent	Permanent imbalance Highly invasive

Results:

Our results with this group of patients after interval-treatment or single-shot application of intratympanic gentamicin demonstrate the effectiveness of this treatment modality without morbidity although our experience is still limited, it allows for expanding the indication on early cases of Menière's disease before permanent hearing loss occurs.. Cochleotoxic side effects can be prevented by treatment intervals of one month. A substantial advantage of TTG treatment is low cost, compared to alternative destructive treatments (i.e. vestibular nerve section or labyrinthectomy). Most authors find that the control of vertigo is comparable to vestibular nerve section (about 90%). TTG treatment is also intrinsically of very low risk, especially compared to nerve section. Compared to labyrinthectomy, TTG treatment is also lower in risk because there is no need for general anesthesia.Even cases of bilateral Menière's disease can be treated successfully using this method.

Conclusion

One-shot low-dosage gentamicin is completely effective on controlling vertigo attacks in Ménière's disease and has useful effects on the aural fullness and tinnitus of patients as well. However, even doses as low as 10 mg gentamicin can cause hearing loss. VEMPs and CDP may have only adjunctive role in monitoring therapeutic responses in intratympanic gentamicin therapy.

Dr.K.K.Desarda.

Prof.Emeritus BJMC & Head otolaryhgology

KEM Hospital,

Pune.

REFERENCES:

• Abou-Halawa AS, Poe DS. Efficacy of increased gentamicin concentraion for intratympanic injection therapy in Meniere's disease. Otol Neurotol 23:494-503, 2002
• Adamonis J and others. Electrocochleography and gentamicin therapy for meniere's disease: a preliminary report. Am. J. Otol 21:534-542, 2000
• Bauer PW, MacDonald CB, Cox LC. Intratympanic gentamicin therapy for vertigo in nonserviceable ears. Am J Otolaryngol 2001 Mar-Apr;22(2):111-5
• Beck C, Schmidt CL (1978) Ten years experience with intratympanically applied Streptomycin (gentamicin) in the therapy of morbus Meniere. Arch Otolaryngol 221, 149-152
• Blakely BW. Clinical Forum: A review of intratympanic therapy. Am J. Otol, 18:520-526, 1997
• BOTTRILL I, Wills AD, Mitchell AL. Intratympanic gentamicin for unilateral Meniere's disease: results of therapy. Clin Otolaryngol 2003; 28: 133-41
• Brandtberg K, bergenius J, Tribukait A. Gentamicin treatment in peripheral vestibular disorders other than meniere's disease. ORL 1996;58:277-279
• Casani, A., D. Nuti, S. S. Franceschini, et al. (2005). "Transtympanic Gentamicin and Fibrin Tissue Adhesive for Treatment of Unilateral Meniere's Disease: Effects on Vestibular Function." Otolaryngol Head Neck Surg133(6): 929-35.
• Chia, S. H., A. C. Gamst, J. P. Anderson, et al. (2004). "Intratympanic gentamicin therapy for Meniere's disease: a meta-analysis." Otol Neurotol25(4): 544-52.
• Cureoglu S and others. Effect of parenteral aminoglycoside administration on dark cells in the crista ampularis. Arch Otol HNS 2003:129: 626-628
• Driscoll CL, Kasperbauer JL, Facer GW, Harner SG, Beatty CW. Low-dose intratympanic gentamicin and the treatment of Meniere's disease: preliminary results. Laryngoscope 107(1):83-9, 1997
• Eklund and others. Effect of intratympanic gentamicin on hearing and tinnitus in Meniere's disease. Am J. Otol 20:350-356, 1999
• Flanagan, S., P. Mukherjee and J. Tonkin (2005). "Outcomes in the use of intra-tympanic gentamicin in the treatment of Meniere's disease." J Laryngol Otol: 1-5.
• Gabra N, Saliba I. The Effect of Intratympanic Methylprednisolone and Gentamicin Injection on Meniere's Disease. Otolaryngol Head Neck Surg. 2013 Jan 11. [Epub ahead of print].
• Gode S, Celebisoy N, Akyuz A, Gulec F, Karapolat H, Bilgen C, Kirazli T. Single-shot, low-dose intratympanic gentamicin in Ménière disease: role of vestibular-evoked myogenic potentials and caloric test in the prediction of outcome. Am J Otolaryngol. 2011 Sep-Oct;32(5):412-6. Epub 2010 Sep 18.
• Hanson HV (1951). The treatment of endolymphatic hydrops (Meniere's disease) with Streptomycin . Ann ORL 60, 676-691
• Harner, S. G., C. L. Driscoll, et al. (2001). Long-term follow-up of transtympanic gentamicin for Meniere's syndrome. Otol Neurotol 22(2): 210-4.
• Helling K, Schönfeld U, Clarke AH. Treatment of Ménière's Disease by Low-Dosage Intratympanic Gentamicin Application: Effect on Otolith Function.Laryngoscope. 2007 Sep 28;
• HOFFER ME, Allen K, Kopke RD, Weisskopf P, Gottshall K, Wester D. Transtympanic versus sustained-release administration of gentamicin: kinetics, morphology, and function. Laryngoscope 2001; 111: 1343-57.

Dr. K.K.Desarda.

Prof.Emeritus B.J.Medical college  & Head otolaryngology

KEM Hospital

Pune

14^th Jan 2020

Tonsillitis diagnosis and treatment

Long term effects of low dose gentamicin in unilateral Meniere/s disease - our choice.

           LONG-TERM  RESULTS  OF  LOW DOSE GENTAMICIN IN UNILATERAL                                                               MENIERE’S  DISEASE.                                                       

                                 (KEM HOSPITAL PUNE STUDY  2010 to 2016)

Abstract

Recently, the "low dose" protocol with just one or two injections in total spaced 1 month apart, has become the standard treatment for Menieres Disease with gratifying results.

Chemical perfusion of the inner ear is an increasingly popular treatment for Ménière's disease.

 The author reports on the long-term results of 50 patients treated with gentamicin delivered via a round window . Patients with Ménière's disease underwent intra-cochlear infusion of low  gentamicin  (10 mg/ml)  through round window niche  approache. Vertigo was controlled in 95 per cent, whilst preserving hearing in 90 per cent. Of patients. . Tinnitus and aural fullness remained improved in 85 percent.

 Long-term vertigo control can be achieved using low dose gentamicin, whilst preserving hearing and vestibular function in the majority of patients.. The procedure is not (very) painful a  local  anesthetic is used to numb the ear drum. A drop of phenol on the ear drum is one method. Another is a topical anesthetic such as "Emla" cream. Or 10% xylocaine spray. The drug is injected, through RW niche and  left in the middle ear for 30 minutes while the person is lying quietly, and then an attempt is made to clear it from the middle ear via the ET tube (with swallowing and "popping" the ear)..

Keywords: Ménière's Disease, Gentamicin, glycerol CDP

INTRODUCTION

Ménière's disease is a clinical disorder defined as the idiopathic syndrome of endolymphatic hydrops.¹ It is an obvious finding that the Ménière's patients rated their quality of life (QoL) significantly worse in both the physical and psychosocial dimensions than the normal healthy subjects. Previous studies have shown that vertigo has more impact on the physical aspects, whereas tinnitus and hearing loss seemed to influence the psychosocial and emotional aspects more than the physical aspects.² There is no cure for Ménière's disease and interventions do not eliminate the underlying cause of it.

In recent decades, intratympanic gentamicin administration for treatment of Ménière's disease has gained widespread popularity and has demonstrated its clinical effectiveness in the control of intractable vertigo associated with Ménière's disease in a variety of clinical studies.^3, 4 Different methods of administration with gentamicin include multiple daily dosing, weekly administration for four total treatments, low-dose therapy consisting one to two injections month apart with repeating treatment only for recurrent vertigo symptoms,  Although numerous articles have been published using each of these techniques, to date there is no agreement between the otolaryngologists regarding which technique offers the greatest amount of vertigo control with the lowest rate of complications.⁵ According to the concept of partial vestibular ablation, only reduction in vestibular function may be enough in most patients to control the vestibular symptoms of the disease.⁵ However, a recent meta-analysis have shown that the low-dosage method, in contrast, trends toward worse effective vertigo control than the other methods.³

Newer techniques such as the computerized dynamic posturography (CDP) have facilitate objective evaluation of patients with balance disorders. This technique allows analysis of the information supplied by the three sensory systems (i.e. visual, vestibular and proprioceptive) which contribute to the maintenance of balance. CDP has been shown to be a cost-effective and useful technique for the characterization and monitoring of patients with balance disorders.⁶

Materials and Methods

In a prospective clinical study, 50 patients with unilateral definite Ménière's disease according to the definition of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS)⁸ were included in the study from January 2010 to February 2016. Criteria for offering intratympanic gentamicin as a treatment option included intractable vertigo despite lifestyle modification and drug-therapy (2 g per day sodium diet, diuretics and betahistine) for at least 6 months no symptoms suggestive of auditory or vestibular disease in the contralateral ear, and serviceable hearing in the contralateral ear. No patient had history of previous ear surgery, neurologic disorder or aminoglycoside sensitivity.

 At the beginning of study, after explanation of treatment efficacy and probability of complications including dead ear and balance problems such as “curative vertigo”,⁹ each patient gave written informed consent for treatment with intratympanic gentamicin. Pretreatment evaluation included a complete neuro-otologic evaluation, magnetic resonance imaging (MRI), pure tone average (PTA) measurement and impedance audiometry  SISI score  Tone decay  and Glycerol test were recorded. An arbitrary scoring system (0 = none, 1 = mild, 2 = moderate, 3 = severe) used for aural fullness and tinnitus grading.

Ten minutes before the injection, the tympanic membrane was anesthetized with topical 10% xylocaine spray. During the procedure, each patient lay supine and the tympanic membrane of the involved ear was visualized under the operating microscope with the head turned 45 degree to the opposite side to prevent leakage of the solution through the Eustachian tube and to allow for adequate contact of the drug with round window membrane. The 0.5 ml of the stock buffered  gentamicin solution (10 mg/ml) was drawn into a tuberculin syringe and with a  27-gauge, 1.5" slightly bent  needle was injected posterioinferiorly. After the injection, the patient maintained this head position for at least 45 minutes and was told to avoid swallowing to prevent any opening of the Eustachian tube. Few patients experienced some burning pain lasted seconds and resolved immediately

Patients were asked to consider water precautions for two weeks and return for initial follow-up after four weeks. In this follow-up session, the frequency of vertigo, functional level, aural fullness and tinnitus changes and severity of these symptoms were recorded and audiometry, was repeated. Patients were also asked to return after two months for follow up.

However in our study, using one-shot low-dosage gentamicin led to complete vertigo cessation  in 95% of the patients In the second follow-up, 75% of our patients reported decrease in both aural fullness and tinnitus. Similar findings regarding fullness have been reported previously,²⁰ but our results about tinnitus decrease were striking. Some investigators have proposed that gentamicin exerts its effects primarily not only on the sensory hair cells but also on the destruction of the dark cells within the labyrinth that are responsible for endolymph production. Thus, the effect of gentamicin should be due to not only destruction of vestibular function but also relieving endolymphatic hydrops.¹⁶

Glycerol Positive test clinically confirms endolymphatic hydrops.Patient will have 30 to 40% good hearing and 80 to 90% vertigo control.A positive test would be contra indicated for Labyrinthectomy. Negative test result is indicative of no post op hearing gain and vertigo control and will be contra indicated  for endolymphatic sac surgery

The advantages of dehydration testing cannot be ignored. Such testing can easily be incorporated into a clinical test battery for the diagnosis of Meniere's disease .

Gentamicin vs. steroids vs. vestibular nerve section

There are some complex judgements that come up when one needs to have "something done" about Meniere's disease. Essentially, it comes down to cost vs. benefit

Method	Hearing Risk	Effectiveness	Durability	Other considerations
Steroid injection	Minimal	Moderate	3 months	Not a logical treatment as doesn't last.
Low dose Gentamicin	Minimal	High	Moderate (1-2 yr)	Best choice
High dose gentamicin	Moderate	High	Usually permanent	Permanent imbalance not unusual
Labyrinthectomy	sure loss	High	Permanent	Permanent imbalance AND hearing loss AND highly invasive
Vestibular nerve section	Moderate	High	Permanent	Permanent imbalance Highly invasive

 

Results:

Our results with this group of patients after interval-treatment or single-shot application of intratympanic gentamicin demonstrate the effectiveness of this treatment modality without morbidity although our experience is still limited, it allows for expanding the indication on early cases of Menière's disease before permanent hearing loss occurs.. Cochleotoxic side effects can be prevented by treatment intervals of one month. A substantial advantage of TTG treatment is low cost, compared to alternative destructive treatments (i.e. vestibular nerve section or labyrinthectomy). Most authors find that the control of vertigo is comparable to vestibular nerve section (about 90%). TTG treatment is also intrinsically of very low risk, especially compared to nerve section. Compared to labyrinthectomy, TTG treatment is also lower in risk because there is no need for general anesthesia.Even cases of bilateral Menière's disease can be treated successfully using this method.

Conclusion

One-shot low-dosage gentamicin is completely effective on controlling vertigo attacks in Ménière's disease and has useful effects on the aural fullness and tinnitus of patients as well. However, even doses as low as 10 mg gentamicin can cause hearing loss. VEMPs and CDP may have only adjunctive role in monitoring therapeutic responses in intratympanic gentamicin therapy.

Dr.K.K.Desarda.

Prof.Emeritus BJMC & Head otolaryhgology

KEM Hospital,

Pune.

REFERENCES:

• Abou-Halawa AS, Poe DS. Efficacy of increased gentamicin concentraion for intratympanic injection therapy in Meniere's disease. Otol Neurotol 23:494-503, 2002
• Adamonis J and others. Electrocochleography and gentamicin therapy for meniere's disease: a preliminary report. Am. J. Otol 21:534-542, 2000
• Bauer PW, MacDonald CB, Cox LC. Intratympanic gentamicin therapy for vertigo in nonserviceable ears. Am J Otolaryngol 2001 Mar-Apr;22(2):111-5
• Beck C, Schmidt CL (1978) Ten years experience with intratympanically applied Streptomycin (gentamicin) in the therapy of morbus Meniere. Arch Otolaryngol 221, 149-152
• Blakely BW. Clinical Forum: A review of intratympanic therapy. Am J. Otol, 18:520-526, 1997
• BOTTRILL I, Wills AD, Mitchell AL. Intratympanic gentamicin for unilateral Meniere's disease: results of therapy. Clin Otolaryngol 2003; 28: 133-41
• Brandtberg K, bergenius J, Tribukait A. Gentamicin treatment in peripheral vestibular disorders other than meniere's disease. ORL 1996;58:277-279
• Casani, A., D. Nuti, S. S. Franceschini, et al. (2005). "Transtympanic Gentamicin and Fibrin Tissue Adhesive for Treatment of Unilateral Meniere's Disease: Effects on Vestibular Function." Otolaryngol Head Neck Surg133(6): 929-35.
• Chia, S. H., A. C. Gamst, J. P. Anderson, et al. (2004). "Intratympanic gentamicin therapy for Meniere's disease: a meta-analysis." Otol Neurotol25(4): 544-52.
• Cureoglu S and others. Effect of parenteral aminoglycoside administration on dark cells in the crista ampularis. Arch Otol HNS 2003:129: 626-628
• Driscoll CL, Kasperbauer JL, Facer GW, Harner SG, Beatty CW. Low-dose intratympanic gentamicin and the treatment of Meniere's disease: preliminary results. Laryngoscope 107(1):83-9, 1997
• Eklund and others. Effect of intratympanic gentamicin on hearing and tinnitus in Meniere's disease. Am J. Otol 20:350-356, 1999
• Flanagan, S., P. Mukherjee and J. Tonkin (2005). "Outcomes in the use of intra-tympanic gentamicin in the treatment of Meniere's disease." J Laryngol Otol: 1-5.
• Gabra N, Saliba I. The Effect of Intratympanic Methylprednisolone and Gentamicin Injection on Meniere's Disease. Otolaryngol Head Neck Surg. 2013 Jan 11. [Epub ahead of print].
• Gode S, Celebisoy N, Akyuz A, Gulec F, Karapolat H, Bilgen C, Kirazli T. Single-shot, low-dose intratympanic gentamicin in Ménière disease: role of vestibular-evoked myogenic potentials and caloric test in the prediction of outcome. Am J Otolaryngol. 2011 Sep-Oct;32(5):412-6. Epub 2010 Sep 18.
• Hanson HV (1951). The treatment of endolymphatic hydrops (Meniere's disease) with Streptomycin . Ann ORL 60, 676-691
• Harner, S. G., C. L. Driscoll, et al. (2001). Long-term follow-up of transtympanic gentamicin for Meniere's syndrome. Otol Neurotol 22(2): 210-4.
• Helling K, Schönfeld U, Clarke AH. Treatment of Ménière's Disease by Low-Dosage Intratympanic Gentamicin Application: Effect on Otolith Function.Laryngoscope. 2007 Sep 28;
• HOFFER ME, Allen K, Kopke RD, Weisskopf P, Gottshall K, Wester D. Transtympanic versus sustained-release administration of gentamicin: kinetics, morphology, and function. Laryngoscope 2001; 111: 1343-57.

Dr. K.K.Desarda.

Prof.Emeritus B.J.Medical college  & Head otolaryngology

KEM Hospital

Pune

10^th August 2016