10.14639/0392-100X-suppl.1-43-2023-11
Information about failure and relapses is critical in deciding whether and how to treat a given condition, as well as during patient counselling before therapy. This paper aims to perform a non-systematic review of relapses and failure of dysphonia treatment in the adult population. Studies on failure and relapses after treatment of benign vocal fold lesions, functional dysphonia and neurogenic dysphonia were analysed. The frequency and the duration of follow-up were heterogeneous, and the management of relapses was reported in only a portion of the studies. Relapses after surgical treatment of benign vocal fold lesions ranged between 1% and 58% of cases, and their management was mainly surgical. Rates of relapse after voice therapy for functional dysphonia and spasmodic dysphonia were 12%- 88% and 8%-63%, respectively. Rates of relapse after surgical treatment for unilateral and bilateral vocal fold paralysis were 10%-39% and 6%-25%, respectively; treatment was mainly represented by surgical revision. In conclusion, failure and relapses of functional and organic dysphonias after therapy are not rare, but treatment modalities are seldomly reported. The data from this non-systematic review stresses the need for further research in this area.
text/xml
1827-675X
2613
en
Antonio Schindler
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
functional dysphonia
Treatment of relapsing functional and organic dysphonia: a narrative literature review
Text.Serial.Journal
https://www.actaitalica.it/
43
Annual congress report
2023-04-21
2023-04-21
2023-04-28
2023-04-28
S84-S94
1
Antonio Schindler
2023/04/21
10.14639/0392-100X-suppl.1-43-2023-11
S84
Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
1827-675X
functional dysphonia
S94
Treatment of relapsing functional and organic dysphonia: a narrative literature review
https://www.actaitalica.it/article/download/2613/948
43
ACTA OTORHINOLARYNGOLOGICA ITALICA 2023;43(SUPPL.1):S84-S94; doi: 10.14639/0392-100X-suppl.1-43-2023-11




Head and Neck section


Treatment of relapsing functional
and organic dysphonia: a narrative literature review
Trattamento delle disfonie funzionali e organiche recidivanti: una review narrativa
Carlo Robotti1, Francesco Mozzanica2, Maria Rosaria Barillari3, Marcella Bono4, Giancarlo Cacioppo4,
Francesca Dimattia4, Marco Gitto4, Sara Rocca4, Antonio Schindler4
1
 Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy; 2 Department of
Otorhinolaryngology, San Giuseppe Hospital, IRCCS Multimedica, Milan, Italy; 3 Department of Mental and Physical Health and
Preventive Medicine, University of “Luigi Vanvitelli”, Naples, Italy; 4 Department of Biomedical and Clinical Sciences, University of
Milan, Milan, Italy


SUMMARY
Information about failure and relapses is critical in deciding whether and how to treat a
given condition, as well as during patient counselling before therapy. This paper aims to
perform a non-systematic review of relapses and failure of dysphonia treatment in the adult
population. Studies on failure and relapses after treatment of benign vocal fold lesions,
functional dysphonia and neurogenic dysphonia were analysed. The frequency and the du-
ration of follow-up were heterogeneous, and the management of relapses was reported in
only a portion of the studies. Relapses after surgical treatment of benign vocal fold lesions
ranged between 1% and 58% of cases, and their management was mainly surgical. Rates of
relapse after voice therapy for functional dysphonia and spasmodic dysphonia were 12%-
88% and 8%-63%, respectively. Rates of relapse after surgical treatment for unilateral and
bilateral vocal fold paralysis were 10%-39% and 6%-25%, respectively; treatment was
mainly represented by surgical revision. In conclusion, failure and relapses of functional
and organic dysphonias after therapy are not rare, but treatment modalities are seldomly
reported. The data from this non-systematic review stresses the need for further research
in this area.
KEY WORDS: relapse, failure, organic dysphonia, functional dysphonia
                                                                                                  Received: January 15, 2023
                                                                                                  Accepted: January 21, 2023
RIASSUNTO
La conoscenza del possibile fallimento terapeutico e delle recidive è cruciale per decidere       Correspondence
se e come trattare una patologia, così come nel counseling del paziente. Questo lavoro si         Antonio Schindler
propone di affrontare una revisione non sistematica dei fallimenti e delle recidive dopo          Department of Biomedical and Clinical Sciences,
trattamento della disfonia nell’adulto. Sono stati analizzati diversi lavori in tema di lesioni   University of Milan, via GB Grassi 74, Milan, Italy
                                                                                                  E-mail: antonio.schindler@unimi.it
cordali benigne, disfonia funzionale e disfonia neurogena. La frequenza e la durata del
follow-up sono eterogenee, e la gestione delle recidive è descritta solo in alcuni lavori.
Le recidive dopo chirurgia per lesioni benigne variano tra l’1% e il 58% dei casi, e sono           How to cite this article: Robotti C, Mozzanica
gestite primariamente mediante revisione chirurgica. I tassi di recidiva dopo logopedia             F, Barillari MR, et al. Treatment of relapsing
per disfonia funzionale e disfonia spasmodica sono pari a 12%-88% e 8%-63%, rispetti-               functional and organic dysphonia: a narra-
vamente. Le recidive dopo chirurgia per paralisi cordale unilaterale e bilaterale sono pari         tive literature review. Acta Otorhinolaryngol
                                                                                                    Ital 2023;43(SUPPL.1):S84-S94. https://doi.
a 10%-39% e 6%-25%, rispettivamente; la loro gestione è eminentemente chirurgica. In
                                                                                                    org/10.14639/0392-100X-suppl.1-43-2023-11
conclusione, i fallimenti e le recidive delle disfonie funzionali e organiche dopo terapia non
sono infrequenti, ma le relative modalità di trattamento non sono spesso descritte. Le ana-
                                                                                                  © Società Italiana di Otorinolaringoiatria
lisi della presente revisione non sistematica sottolineano la necessità di ulteriori ricerche     e Chirurgia Cervico-Facciale
in questo ambito.
PAROLE CHIAVE: recidiva, fallimento, disfonia organica, disfonia funzionale                                      OPEN ACCESS

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                                                                                                  article can be used by giving appropriate credit and mentio-
Introduction                                                                                      ning the license, but only for non-commercial purposes and
                                                                                                  only in the original version. For further information: https://
Dysphonia is a symptom due to an impairment of voice production and charac-                       creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                                                                                  Relapsing dysphonias




terised by the alteration of voice quality or by vocal effort that   of the frequency of relapses and failure of dysphonia treat-
impairs communication and affects quality of life. It has a life-    ment in the adult population.
time prevalence of 29.9% and a point-prevalence of 6.6%. It
impacts working activities as 7.2% of employed adults were           Failure and relapses of benign organic dysphonia
absent from work 1 or more days in the past year because of          Benign organic dysphonias are generally treated with sur-
their voice, and 2% had more than 4 days of voice-related            gery, with the only exception of vocal fold nodules. Al-
absence 1. In clinical practice, dysphonia accounts for up to        though there is general consensus that benign vocal fold
0.26% and 3.2% of visits for general practitioners and otorhi-       lesions should be treated surgically, voice therapy may
nolaryngologists, respectively 2. Several conditions may lead        play a role as an alternative treatment 4,5, or as an adjunc-
to dysphonia, and they can be grouped in three major cate-           tive therapy before or after therapy. However, the role of
gories of voice disorders based on pathophysiology, audito-          voice therapy is controversial and poorly investigated 6-8.
ry-perceptual and visual-perceptual observations: organic,           Nonetheless, when analysing failures and relapses of sur-
functional and neurogenic dysphonias. Organic dysphonias             gical treatment, the potential impact of voice therapy as a
are due to pathologies of laryngeal structures (vocal folds and      complementary treatment should also be considered. In Ta-
laryngeal cartilages) and are usually subdivided into diseases       ble I studies on relapses and their treatment after surgery
of the vocal fold epithelium (papillomatosis, dysplasia, car-        for vocal fold polyps, cysts, Reinke’s oedema and nodules
cinoma), diseases of Reinke’s space (polyps, nodules, cysts,         are reported 9-29. The 9 studies considered in this review on
Reinke’s oedema), and impairments of the laryngeal cartilages        surgical treatment for vocal fold polyps included more than
(as after partial laryngectomy). Functional dysphonias include       1000 patients, with a follow-up raging from 0 to 24 months
impairments in voice production without a laryngeal patholo-         and relapses ranging from 1% to 5%; post-surgical voice-
gy due to a dysfunction of voice behaviour and include muscle        therapy was reported in the majority of studies (7/9), while
tension dysphonia and psychogenic dysphonia. Neurogenic              treatment of relapses was reported in only three studies,
dysphonias are due to impairment of laryngeal movements              being surgical in all cases. The 6 studies considered in this
because of diseases affecting either the peripheric (vagal or        review on surgical treatment for vocal fold cysts included
recurrent laryngeal nerve impairment) or central nervous sys-        less than 1000 patients, with a follow-up of 0-54 months
tem (such as spasmodic dysphonia or tremor). Organic, func-          and relapses ranging from 2% to 5%; post-surgical voice-
tional and neurogenic dysphonia represent 18.8%, 43.7% and           therapy was reported in more than half of studies (7/9),
37.3% of the Italian population seeking treatment for dyspho-        while only one study reported the treatment of relapses,
nia, respectively; multidimensional voice analysis showed that       being surgical. The 5 studies considered in this review on
neurogenic dysphonia generally presents more severe voice            surgical treatment for Reinke’s oedema included over 600
impairment compared to organic and functional dysphonia 3.           patients, with a follow-up raging from 0 months to 8 years
An additional condition often encountered in otorhinolaryn-          and relapses ranging from 2% to 58%; post-surgical voice-
gological clinical practice with potential effects on voice is       therapy was reported in 3 of 5 studies, while treatment of
Laryngo-pharyngeal Reflux Disease (LPRD).                            relapses (surgical) was reported only in one study.
Different treatments are now available for dysphonia in-             With regards to the management of vocal fold nodules, sev-
cluding pharmacological (steroids, anti-reflux medica-               eral areas of uncertainty remain, including poorly defined
ments, botulinum toxin injection), surgical (microsurgical           nomenclature, the natural history of paediatric vocal nod-
removal of laryngeal lesions, laryngeal framework surgery,           ules, the establishment of criteria to measure successful treat-
filler injection) and behavioural therapy (voice therapy) 4,5.       ment, optimal configuration of speech therapy regimens and
While several studies aimed to analyse the safety and ef-            the rationale for surgical intervention; nonetheless, there is
ficacy of the available treatments, little is known about fail-      general consensus that vocal fold nodules should be treated
ure and relapses. Relapses consist in the return of a disease        primarily through voice therapy. A recent systematic search
or its signs and symptoms after a period of improvement,             on the effectiveness of voice therapy in adult patients with
while failure is defined as the lack of success or the inabil-       vocal fold nodules retrieved 9 papers 30. Although the study
ity to meet an expectation. Information about failures and           design and the evidence levels were low, all studies reported
relapses is critical in deciding whether and how to treat a          positive effects of voice therapy on different vocal param-
given condition, and it is crucial during patient counsel-           eters (perceptual, acoustic and self-assessment scores), but
ling before therapy. In particular, clear patient information        no data regarding the number of failures was reported. Data
about failure and relapses will avoid inappropriate discus-          on the time interval between end of treatment and vocal fold
sions and requests, including legal issues, after treatment.         nodules reduction or resolution was not available. Only in
The aim of this paper is to perform a non-systematic review          the study by Chernobelsky 28, conducted on 28 patients who



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Table I. Rates of failure and relapses after surgery for vocal fold polyps, cysts, Reinke’s edema, and nodules.
 Disease           Author, year            Patients           Follow-up            Relapses (%)        Post-surgical voice      Relapses treatment
                                                                 length                                      therapy
 Polyp               Bouchayer et al.,            267                n/a            3/267 (1.12%)        267 (100%)                      n/a
                          1992 9
                      Hochman et al.,             40            2-24 months          1/40(1.25%)         35 (87.5%)                    Surgery
                          2000 10
                     Ju et al., 2013 11           118            3 months           7/118 (5.9%)         55 (46.6%)                      n/a
                       Byeon et al.,              280           6-12 months         11/280 (3.9%)        18 (0.36%)                      n/a
                          2013 12
                       Zhang et al.,              60                 n/a            2 /60 (3.33%)             n/a                      Surgery
                          2015 13
                       Barillari et al.,          70             12 months           4/70 (5.7%)          70 (100%)                      n/a
                          2017 14
                      Agarwal et al.,             120            5.5 months         4/120 (3.3%)        68/91 (74,7%)                    n/a
                          2019 15
                    Lee et al., 2020 16           235            13.7 ± 22.3,      14/235 (5,53%)            69%                    7 Voice therapy
                                                                 (0.1- 119.8)                                                          7 Surgery
                                                                    months                                                   10 Voice therapy and surgery
                       Patrial et al.,            396           0-210 months        20/396 (5.5%)             n/a                         n/a
                         2020 17
 Cyst                Bouchayer et al.,            494                n/a            12/494 (2.4%)      494/494 (100%)                    n/a
                          1992 9
                       Chang et al.,              21              3 months           1/21 (4.8%)              n/a                        n/a
                         2003 18
                    Hsu et al., 2009 19           25              12 months           1/25 (4%)              n/a                         n/a
                      Tibbetts et al.,            21             5.5 (0.1-54)        1/21 (4.8%)        14/21 (66.7%)                  Surgery
                         2018 20                                   months
                    Lee et al., 2019 16           92              13.7 (0.1-         2/92 (2.2%)             69%                         n/a
                                                                119.8) months
                      Patrial et al.,             349           0-210 months        6/349 (1.7%)              n/a                        n/a
                         2020 17
 Reinke’s             Nielsen et al.,             111           6 months - 8        64/111 (58%)       55/111 (49.5%)                  Surgery
 edema                   1986 21                                   years
                      Bouchayer et                138               n/a             3/138 (2.29%)      138/138 (100%)                    n/a
                        al.,1992 9
                     Goswami et al.,              92             12 months          4/92 (4.35%)        92/92 (100%)                     n/a
                         2003 22
                     Tasar, 2013 23               21              6 months          1/21 (4.7%)               n/a                        n/a
                      Patrial et al.,             261           0-210 months        8/261 (3.1%)              n/a                        n/a
                         2020 17
 Nodules              Nagata et al.,       372: 72 surgery      Over 5 months     4/36 (11%) surgery        0/372                        n/a
                         1983 24           300 conservative                         34/101 (33%)
                      Lancer et al.,             34                5 years           9/34 (26%)          20/34 (59%)                     n/a
                         1988 25
                      Murry et al.,         39 voice therapy      11/39 voice        9/39 (23%)               n/a                        n/a
                         1992 26           20 surgery & voice   therapy 20/20        4/20 (20%)
                                                therapy            (3 months)
                      Zeitels et al.,             119            Individualised     4/119 (3.2%)       119/119 (100%)               Microsurgery
                         2002 27
                    Chernobelsky et         28 voice therapy    Over 10 years       22 relapses 6             n/a                        n/a
                       al., 2007 28                                                    failures
                    Bequignon et al.,             62              9.5 (5-15)        20/62 (32%)            46 (51%)                      n/a
                         2013 29                                    years




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                                                                                                                                       Relapsing dysphonias




underwent voice therapy, some information on relapses and                         injection with a variety of fillers, laryngeal framework sur-
failures was available; over a 10-year period, relapses were                      gery and laryngeal re-innervation; however, no consensus
22/28 (78%) and failures were 6/28 (21%). The 5 studies                           exists on which is the most effective treatment, or on the
considered in this review on surgical treatment for vocal fold                    selection and timing for surgical or behavioural therapy.
nodules included overall over 300 patients, with a follow-up                      A recent systematic review analysed several studies on the
ranging from 5 months to 15 years and relapses ranging from                       efficacy of voice therapy for UVFP, showing a general im-
3% to 33%; post-surgical voice-therapy was reported in 4                          provement in voice, which is maintained for up to 1-year 38.
of 5 studies, while only one study reported the treatment of                      However, no data on failure or relapses was reported. Only
relapses, being surgical.                                                         one study analysed the need for surgery after voice thera-
                                                                                  py: over 60% of the patients who underwent voice therapy
                                                                                  for UVFP were satisfied with the results and did not re-
Failure and relapses of functional dysphonia
                                                                                  quire any additional treatment 39. In Table III the studies on
Functional dysphonias are generally treated through voice                         failures and relapses and their treatment after surgery for
therapy. Although there is now evidence on the efficacy of                        UVFP are reported 40-51. Two studies conducted on almost
voice therapy in this group of patients, little is known on                       140 patients, investigating the efficacy of injection laryngo-
relapses and failures. In Table II the studies on relapses and                    plasty with a follow-up up to 36 months, reported relapses
their treatment after voice therapy for muscle tension dys-                       in 10%-35% of cases; voice therapy was prescribed for all
phonia and psychogenic dysphonia are reported 31-37. The                          patients with relapses who underwent additional surgery,
4 studies considered in this review on muscle tension dys-                        being reinjections in most cases. Eight studies on a total
phonia included less than 100 patients with failures ranging                      of over 1000 patients who underwent laryngeal framework
from 12% to 68%; data on failure and/or relapses manage-                          surgery, with a follow-up range of 1-132 months, reported
ment was not available 31-34. The 3 studies on psychogenic                        relapses in 10%-18% of cases; data on voice therapy after
dysphonia included 81 patients with failures or relapses                          surgery was not available, but all patients with relapses un-
ranging from 50% to 88%; data on failure and/or relapses                          derwent revision laryngeal framework surgery with a va-
management were available in 2 of the 3 studies and always                        riety of surgical techniques. Finally, two studies analysed
included the involvement of a psychologist 35-37.                                 failure and relapses after laryngeal re-innervation; patients
                                                                                  undergoing this surgery are still limited, and failures could
                                                                                  be managed with either laryngeal framework surgery or la-
Failure and relapses of neurogenic dysphonia
                                                                                  ryngeal injection.
Unilateral vocal fold paralysis
Different treatments are now available for unilateral vocal                       Bilateral vocal fold paralysis
fold paralysis (UVFP) including voice therapy, laryngeal                          Laryngeal dyspnoea due to bilateral vocal fold paralysis


Table II. Rates of failure and relapses after voice therapy for muscle tension dysphonia and psychogenic dysphonia.
 Disease                   Author,           Patients                 Treatment                      Treatment                     Relapses
                            year                                  duration/follow-up            failure/relapses (%)              management
 Muscle tension         Roy et al.,           25                     1 session                        13/19
 dysphonia                1997 31
                       Carding et al.,        45                      8 weeks                      7/45 (15%)
                          1999 32
                         Lee et al.,           8                   1-2.5 months                     1/8 (12.5)
                          2005 33
                       Ogawa et al.,          23                     1 session                    5/23 (21.7%)
                          2013 34
 Psychogenic           Butcher et al.,        19                        n/a                            6/12            Joint therapy with a speech therapist
 dysphonia                1987 35                                                                                      and a psychologist with a cognitive-
                                                                                                                               behavioural approach
                       Reiter et al.,          8                  16 (± 8) months                  7/8 (88.5%)                          n/a
                         2013 36
                      Tezcaner et al.,        54           21.4 (± 3.7) months follow-up           10/20 (50%)               Psychological follow-up
                         2019 37




                                                                                                                                                       S87
C. Robotti et al.




Table III. Rates of failure and relapses after surgery for UVFP.
 Author,                                        Follow-up                   Relapses               Post-surgical
                             Patients                                                                                                      Relapses treatment
 year                                             lenght                      (%)                  voice therapy
 Havas et al.,              51 (12 laryngeal                                                                               Not specified. 4 had TP following reinnervation, 4
                                                     24 months           18/51 (35.3%)                   n/a
 1999 40                     reinnervation)                                                                                     had TP following injection aumentation
                                                                                                                            TP1 45/406 (11.1%); TP2 1/10 (10%), TP3 3/8
 Maragos,
                                331, LFS                 n/a            48/331 (14.5%),                  n/a              (37.5%); TP4 5/45 (11.1%), AA 5/142 (3.5%); AF
 2001 41
                                                                                                                                              2/17 (11.8)
                                                                                                                            Revision ML + AA 9/20 (45%), implant removal
 Woo et al.,                                         0.5 – 132
                                 n/a, LFS                                       20                       n/a              4/20 (20%), revision ML 2/20 (10%), lipoinjection
 2001 42                                              months
                                                                                                                                      2/20 (10%), AA 3/20 (15%)
                                                                                                                             Revision Gore-Tex ML 9/22 (40,9%), injection
 Cohen et al.,
                                156, LFS            1-15 months         16/156 (10.2%)                   n/a              augmentation 9/22 (40,9%), implant removal 2/22
 2004 43
                                                                                                                                      (9,09%), AA 2/22 (9,09%).
                                                                                                                           Injection ML prior to revision ML in 14/48 (29%)
                                                                                                                              surgeries. 28 AUG; 1 arytenopexy; 3 AUG +
 Parker et al.,
                                208, LFS            14.6 months         39/208 (18.7%)                   n/a               arytenopexy; 1 AUG + cricothyroid subluxation; 2
 2015 44
                                                                                                                          arytenopexy + cricothyroid subluxation; 11 AUG +
                                                                                                                                arytenopexy + cricothyroid subluxation.
 Kwak et al.,
                                  40 TP             46.5 months            6/40 (15%)                    n/a                                    6 revision TP
 2016 45
                                                                        14 (10,4%): 5/56                                    6 removal of old implant + new implant + AA; 3
                                                                         (8.9%) of those                                   removal of old implant + new implant; 1 addition
                            135 ML (56 with
 Silva Merea et al.,                                                      with prior IA +                                   of new implant; 1 removal of old implant + new
                             prior injection           unclear                                           n/a
 2018 46                                                                  9/79 (11.4%)                                    implant + contralateral medialisation; 1 removal of
                             augmentation)
                                                                         of those with no                                 old implant + new implant + AA + pharyngoplasty;
                                                                              prior IA                                             1 partial removal of implant + AA
                              n/a. Previous
 Marie et al.,
                                TP or VF             36 months                   8                       n/a               8 unilateral laryngeal reinnervation (ansa to RLN)
 2020 47
                              augmentation
 Prstačić et al.,                                    12 months                                       Before fat
                                  78, IA                                  8/78 (10.3%)                                                 Second surgery not specified
 2020 49                                              (unclear)                                    augmentation
 Kishimoto et al.,                                                                                                            Revision framework surgery (TP1 13; AA 5;
                                   149             1-109 months          19 pz (12,75%)                  n/n
 2020 48                                                                                                                                TP1+TP4 1; TP1+AA 2)
 Mes et al.,
                                 61, LFS            >12 months               6 (9.8%)                    n/a                    3 additional AA, 3 injection augmentation
 2021 50
 Miaśkiewicz et
                                  51, IA             36 months             18/51(35%)                    yes                                   18 reinjections
 al.,2021 51
TP: Thyroplasty; AA: Arytenoid adduction; AF: arytenoid fixation; AUG: anterior augmentation; LFS: laryngeal framework surgery, ML: medialisation laryngoplasty, IA: injection augmen-
tation; n/a: not available; RLN; recurrent laryngeal nerve.



can be managed through a variety of surgical techniques,                                      nificantly improve any voice parameter in patients with
aiming to maintain oral respiration and limiting the im-                                      spasmodic dysphonia. Several other effective treatments
pact on voice production. In Table IV the studies regard-                                     are currently available, including botulinum toxin injec-
ing failures and relapses and their treatment after surgery                                   tion and a range of surgical approaches, such as thyroar-
for bilateral vocal fold paralysis are reported 52-74. In the                                 ytenoid myoneurectomy, thyroplasty type II (without or
23 studies on almost 580 patients who underwent surgery,                                      with a titanium bridge), selective laryngeal adductor den-
with a follow-up up of 3-60 months, relapses were reported                                    ervation-reinnervation and laryngeal nerve resection. Bot-
in 6%-25% of cases; voice therapy was not prescribed in                                       ulinum injection is the most widely applied treatment by
any of the studies; treatment of relapses was reported in 8                                   both otorhinolaryngologists and neurologists, but should
of 23 studies, and in 7 of them it was revision surgery.                                      be repeated approximately every 3-4 months. Surgical ap-
                                                                                              proaches are more invasive, but have the potential to achieve
Spasmodic dysphonia                                                                           stabilisation of the disease. In Table V several studies are
There is general agreement that voice therapy can not sig-                                    reported, describing failures and relapses after treatment



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                                                                                                                                   Relapsing dysphonias




Table IV. Rates of failure and relapses after surgery for bilateral vocal fold paralysis.
 Author,                                                                                     Follow-up     Relapses    Post-surgical     Relapses
                                    Primary treatment                    Patients
 year                                                                                         duration       (%)       voice therapy     treatment
 Dennis et al.,
                                     Posterior cordectomy                    6               1-5 years        n/a           no               n/a
 1989 52
 Laccourreye et al.,              Posterior partial transverse
                                                                             25              10 months        n/a           no               n/a
 1999 53                                  cordotomy
 Pia et al.,
                                Posterior ventriculocordectomy               41              43 months        n/a           no               n/a
 1999 54
 Manolopoulos et al.,
                                  Partial posterior cordectomy               18              0.6-6 years   2 (11%)          no         Revision surgery
 1999 55
 Maurizi et al.,                 Subtotal arytenoidectomy and
                                                                             39              30 months     5(12,8%)         no         Revision surgery
 1999 56                          medial-posterior cordotomy
 Hans et al.,
                                Posterior transverse cordotomy               4               24 months        0             no               n/a
 2000 57
 Segas et al.,                   Unilateral posterior ventricular
                                                                             20                 n/a           n/a           no               n/a
 2001 58                                   cordectomy
 Dursun et al.,
                             Posterior transverse laser cordotomy            22             14-48 months   4 (18%)          no         Revision surgery
 2006 59
 Misiolek et al.,             Total arytenoidectomy with posterior
                                                                             30                5 years        0             no               n/a
 2007 60                                   cordectomy
                                 Posterior cordectomy (n = 2),
 Harnisch et al.,
                             laterofixation (n = 1), posterior trans-        10             6-57 months    1 (10%)          yes        Revision surgery
 2008 61
                                     verse cordotomy(n = 7)
 Bajaj et al.,                                                                                                                          Conservative
                              Bilateral posterior vocal fold release         9               0.3-4 years    1(11%)          no
 2009 62                                                                                                                                 treatment
 Hyodo et al.,
                                         Laterofixation                      11             3-80 months     1 (9%)          no               n/a
 2009 63
 Ezzat et al.,
                                         Laterofixation                      21               6 months        n/a           no               n/a
 2010 64
                              Unilateral laser posterior cordotomy
                                   (n = 12), bilateral posterior
 Riffat et al.,                   cordotomy (n = 8), combined
                                                                             34              24 months        n/a           no               n/a
 2012 65                       cordotomy and arytenoi- dectomy
                             (n = 9), excision of a posterior glottic
                                            scar (n = 5)
 Yilmaz,                        Total arytenoidectomy, vocal fold
                                                                             50              1-3 years      3(6%)           no         Revision surgery
 2012 66                                   lateralization
                                 Posterior chordotomy, partial or
 Nawka et al.,
                               total arytenoidectomy, permanent              32               6 month         0             no               n/a
 2015 67
                                           laterofixation
 Asik et al.,                   Monolateral posterior transverse
                                                                             11               2 months        0             no               n/a
 2016 68                                     cordotomy
 Fabre et al.,
                                    Vocal fold lateralization                18                 n/a           n/a           no               n/a
 2019 69
 Rashid et al.,
                                      Posterior cordotomy                    34               2 months     6 (17,6%)        no               n/a
 2019 70
 Qazi et al.,
                                Transverse posterior cordotomy               20               442 days     5 (25%)          no         Revision surgery
 2021 71
 Filauro et al.,             Posterior cordotomy (± medial partial
                                                                             33                 n/a        6 (18,1%)        no         Revision surgery
 2021 72                               arytenoidectomy)
 Ghodke et al.,                   Transverse cordotomy with
                                                                             10                 n/a           n/a           no               n/a
 2021 73                        anteromedial arytenoidectomy
 Benninger et al.,
                                 Unilateral coblator cordotomy               94              16 months        n/a           no               n/a
 2022 74




                                                                                                                                                   S89
C. Robotti et al.




Table V. Rates of failure and relapses of spasmodic dysphonia after surgery and botulinum toxin injection.
 Author,                                               Follow-up             Relapses          Post-surgical voice
                       Treatment        Patients                                                                                               Relapses treatment
 Year                                                    lenght                (%)                    therapy
 Aronson et al.,
                             LNR                 33             36 months            21 (63.64%)                     n/a                            Not reported
 1983 75
                                                                                                                                       1/4 (25%) BTX, 1/4 (25%) collagen
 Berke et al.,
                           SLAD-R                21             36 months             4 (19.05%)                     n/a               injection, 1/4 (25%) TMN, 1/4 voice
 1999 76
                                                                                                                                                       therapy
 Smith et al.,
                           BTX-ona               2              3-7 years              2 (100%)                      n/a                        No further treatment
 2000 77
                                                                                   12 (80%) pt had
 Galardi et al.,       BTX-ona, BTX-
                                                 15         3.53 years (1-8)       ³ 1 non effective                 n/a                                 n/a
 2001 78                    abo
                                                                                       injection
 Park et al.,
                           BTX-ona               71              5 years               6 (8.45%)                     n/a                                 n/a
 2003 79
 Isshiki et al.,
                              TPII               25            3-6 months               1 (4.0%)                     n/a                 Revision TPII with TB (1/1, 100%)
 2004 80
 Chhetri et al.,                                                                                                                       5/12 (41.67%) BTX; 7/12 (58.33%)
                           SLAD-R                83             49 months            12 (14.46%)                     n/a
 2006 81                                                                                                                                          not reported
 Cannito et al.,                                                                  7 (16.67%) all over
                           BTX-ona               42             3-6 weeks                                            n/a                                 n/a
 2008 82                                                                            70 years of age
                                                                                                                                       2/7 (28.57%) removal of goretex or
 Sanuki et al.,
                              TPII               90           12-36 months             7 (7.78%)                      1               TB, no revision surgery; 5/7 (71.43%)
 2009 83
                                                                                                                                                      new TB
                                                                                      11 (37.93):
 Su et al.,                                                    31 (12-63)             3 (10.34%)
                             TMN                 29                                                                  n/a                    Revision TMN (7/8, 87.5%)
 2010 84                                                        months               unsuccessful
                                                                                        surgery
 Sanuki et al.,                                                17.6 (7-25)
                              TPII               10                                     0 (0.0%)                     n/a                                   -
 2010 85                                                         months
 Tsuji et al.,                                                  31 (4-96)
                             TMN                 15                                   2 (13.33%)                     n/a                                 n/a
 2012 86                                                         months
 Nomoto et al.,                            65 (30 TMN,
                         TMN vs TPII                            6 months            1 TMN (3.33%)                    n/a                     Revision TMN 1/1 (100%)
 2015 87                                     35 TPII)
 Schuering et al.,
                             TMN                 22             30 months            10 (45.45%)                     n/a                        TMN 10/10 (100%)
 2020 88
 Zhao et al.,
                           BTX-ona              131                 n/a           67 (12%) injections                n/a                                 n/a
 2020 89
 Kohli et al.,
                           BTX-inc               9            2.56 months          4 non responders                  n/a                                 n/a
 2022 90
TMN: thyroarytenoid myoneurectomy; TPII: thyroplasty type II; TB: titanium bridge; SLAD-R: selective laryngeal adductor denervation-reinnervation; LNR: laryngeal nerve resection;
BTX-ona: onabotulinumtoxinA (Botox®); BTX-inc: incobotulinumtoxinA (Xeomin®, “naked” toxin with no surrounding proteins); BTX-abo: abobotulinumtoxinA (Dysport®).



for spasmodic dysphonia and their management 75-90. In the                                  scribed in only one case. The management of failure was
6 studies on 270 patients who underwent botulinum toxin                                     reported in 6 of 10 papers and included several options:
injection, with a follow-up up ranging from 3 months to 7                                   surgical revision (in most cases), botulinum toxin injection
years, failures were reported in 8%-35% of cases, reaching                                  and collagen injection.
a 80% failure rate in at least a single treatment; data on
voice therapy in addition to surgery or for non-responding                                  Failure and relapses of laryngopharyngeal
patients was not reported. No data on management of fail-
ures after botulinum toxin injection was reported. In the 10
                                                                                            reflux
studies on 393 patients who underwent surgical treatment,                                   LPRD is an inflammatory clinical condition affecting the up-
with a follow-up up ranging from 6 to 49 months, failures                                   per aero-digestive tract, causing several symptoms, including
were reported in 3%-63% of cases; voice-therapy was pre-                                    dysphonia. Treatment options mainly include diet and lifestyle



S90
                                                                                                                    Relapsing dysphonias




modifications, associated with proton pump inhibitors (PPIs)          In addition to pathological gastro-oesophageal or pharyn-
and/or alginate or magaldrate. Less frequently prescribed med-        go-laryngeal conditions which may be associated or non-
ications include prokinetic agents, H2 receptor antagonists, or       recognised, several other risk factors related to GERD and
γ-aminobutyric acid derivatives. Surgery (e.g. fundoplication)        LPRD may play a key role in favouring chronic-recurrent
represents a treatment option only in selected patients. Simi-        clinical courses, even in case of thorough diagnostic ap-
lar to Gastro-oesophageal Reflux Disease (GERD) patients,             proaches and adequate treatment regimens. These risk
individuals suffering from LPRD may experience recurrences            factors include: inadequate dietary regimens (lack of ad-
throughout life. Based on the clinical course of the disease,         herence to the Mediterranean diet); high consumption of
three main LPRD subtypes have been recently described: (a)            specific foods (acid or with high protein or fat content);
acute LPRD (29.3%), in case of complete resolution of symp-           poor eating habits; tobacco smoke; alcohol abuse; obesity
toms with no relapses during a 3-year follow-up; (b) recurrent        and overweight; sleep disorders; psychosocial distress 98.
LPRD (40.7%), in case of one or more recurrences followed             Defining the exact recurrence rate with reference to treat-
by a full response to medical treatment or dietary modifica-          ment duration represents an additional issue. Success rates
tions, even if temporary; (c) chronic LPRD (30.0%), in case           of therapy vary between 18% and 87%, but the heterogene-
of chronic clinical course with absent or partial response to         ity of published research and the absence of long follow-
medical therapy, or when patients rapidly relapse if therapy is       up periods (often not longer than 6-12 months) make data
discontinued, thus requiring long-term treatment regimens 91.
                                                                      unhelpful when investigating LPRD recurrences.
With regards to recurrent LPRD, similar data were also found
                                                                      Lastly, even if accurate diagnoses and appropriate therapies
by Koufman and coworkers when analysing data from 225
                                                                      are ensured, an additional confounding factor could be repre-
GERD patients with extra-oesophageal symptoms 92. The au-
                                                                      sented by the scarce compliance of patients towards treatment
thors highlighted a chronic-recurrent clinical course in 25% of
                                                                      (poor adherence to dietary restrictions, inappropriate lifestyle,
patients, even if high doses of PPIs were prescribed. A more
                                                                      inaccurate timing of medications). According to Barrison et
recent study conducted by Verhasselt et al. on 100 LPR pa-
tients during a 3-year follow-up demonstrated a chronic-recur-        al., poor compliance may represent the first reason for thera-
rent clinical course in one-third of cases 93. Nevertheless, treat-   peutic failure and a chronic-recurrent clinical course 99.
ment regimens for recurrences were not described in detail.
The actual success of therapies remains hard to predict.              Conclusions
However, many risk factors have been identified to date
                                                                      Although surgical, pharmacological and behavioural thera-
as potential markers of treatment failure, in terms of both
                                                                      pies for non-oncological voice disorders are widely provid-
absent or incomplete response and increased risk of recur-
                                                                      ed in everyday clinical practice, data on failures and relapse
rence. The most important ones include: hiatal hernia; pro-
                                                                      has been little explored. The frequency and the duration of
longed contact between the mucosa and the acid refluxate
                                                                      follow-up after treatment for non-oncological voice disor-
demonstrated through Hypopharyngeal-Oesophageal Mul-
tichannel Intraluminal Impedance-pH Monitoring (HEMII-                ders are heterogeneous, highlighting the need to develop
pH) 94; celiac disease; proximal oesophageal dysmotility;             consensus in this area. The available data suggests that
achalasia; oesophageal spasms; gastroparesis; food intol-             failures and relapses are not rare; this information should
erances; eosinophilic oesophagitis 95,96. Several authors             be regularly transferred to patients before any therapeutic
provided interesting insights into differential diagnoses,            planning. Treatment of failure and relapses is rarely report-
with particular reference to conditions affecting the head            ed; therefore, at the current state of knowledge, it should be
and neck district which may mimic or overlap with LPRD:               decided on the basis of the experience and the skills of each
chronic rhinosinusitis; autoimmune inflammatory larynge-              team, which should include at the very least a phonosur-
al disorders (e.g. rheumatoid arthritis, Sjögren syndrome,            geon, a phoniatrician and a speech and language patholo-
sarcoidosis, fibromyalgia, musculoskeletal laryngeal disor-           gist. The data from this non-systematic review underlines
ders); aging voice. Similarly, Carroll et al. identified ad-          the urgent need for further research in this area.
ditional cofactors which may be associated with an “appar-
ently” chronic-recurrent clinical course of LPRD: allergic            Conflict of interest statement
rhinitis; asthma; chronic laryngitis; glottic insufficiency;          The authors declare no conflict of interest.
post-viral vagal neuropathies 97. Furthermore, active al-
lergies can interfere with the therapeutic management of              Funding
LPRD, since they may induce laryngeal signs and symp-                 This research did not receive any specific grant from funding
toms which are indistinguishable from those of LPRD.                  agencies in the public, commercial, or non-profit sectors.



                                                                                                                                   S91
C. Robotti et al.




Author contributions                                                               13
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CR: literature review, paper writing, paper corrections;                                vocal fold. Int J Clin Exp Med 2015;8:18265-18274.
FM: literature review, supervision; MRB: literature review,                        14
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paper editing; MB: literature review, paper editing; GC: lit-                           omized clinical trial comparing the treatment of vocal fold polyps via pho-
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                                                                                        training. J Voice 2017;31:379.E13-379.E20. https://doi.org/10.1016/j.
editing; MG: literature review, paper editing; SR: literature                           jvoice.2016.07.002
review, paper editing; AS: supervision, paper writing, paper                       15
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corrections.                                                                            surgery and voice therapy for patients with vocal fold polyps. Laryngo-
                                                                                        scope 2019;129:1067-1070. https://doi.org/10.1002/lary.27697
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Ethical consideration                                                                   after microlaryngoscopy. Laryngoscope 2020;130:1989-1995. https://
Not applicable.                                                                         doi.org/10.1002/lary.28349
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