10.14639/0392-100X-N2395
Objective. Bilateral selective reinnervation of the larynx aims to restore both vocal cord tone and abductor movements in patients with bilateral vocal cord palsy. Methods. Four females and one male treated by bilateral selective reinnervation of the larynx were included in the present study. In all cases, both posterior cricoarytenoid muscles were reinnervated using the C3 right phrenic nerve root through the great auricular nerve graft, while adductor muscle tone was bilaterally restored using the thyrohyoid branches of the hypoglossal nerve through transverse cervical nerve grafts. Results. After a minimum follow-up of 48 months, all patients were successfully tracheostomy free and had recovered normal swallowing. At laryngoscopy, the first patient recovered a left unilateral partial abductor movement, the second had complete bilateral abductor movements, the third did not show improvements of abductor movements, but symptomatology was improved, the fourth recovered partial bilateral abductor movements and the fifth case did not show improvements and needed posterior cordotomy. Conclusions. Bilateral selective laryngeal reinnervation, although a complex surgical procedure, offers a more physiologic recovery in the treatment of bilateral vocal fold paralysis. Selection criteria still needs to be precisely defined to avoid unexpected failures.
text/xml
1827-675X
2395
en
Filippo Carta
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
functional results
Bilateral selective laryngeal reinnervation in patients with bilateral vocal cord palsy
Text.Serial.Journal
https://www.actaitalica.it/
43
Laryngology
2023-05-16
2022-11-27
2023-05-19
2023-05-19
189-196
1
Filippo Carta
2023/05/16
10.14639/0392-100X-N2395
189
Department of Surgery, Unit of Otorhinolaryngology, Azienda Ospedaliero-Universitaria di Cagliari, University of Cagliari, Cagliari, Italy
1827-675X
functional results
en
196
Bilateral selective laryngeal reinnervation in patients with bilateral vocal cord palsy
https://www.actaitalica.it/article/download/2395/988
43
ACTA OTORHINOLARYNGOLOGICA ITALICA 2023;43:189-196; doi: 10.14639/0392-100X-N2395




Laryngology


Bilateral selective laryngeal reinnervation
in patients with bilateral vocal cord palsy
Reinnervazione selettiva bilaterale della laringe nei pazienti con paralisi bilaterale
delle corde vocali
Roberto Puxeddu1,2, Valeria Marrosu1, Marta Filauro3-5, Cinzia Mariani1, Giampiero Parrinello3, Kate Heathcote6,
Clara Gerosa7, Melania Tatti1, Stefano Manca di Villahermosa1, Francesco Mora3,5, Giorgio Peretti3-5, Filippo Carta1
1
  Department of Surgery, Unit of Otorhinolaryngology, Azienda Ospedaliero-Universitaria di Cagliari, University of Cagliari, Cagliari,
Italy; 2 ENT Department, King’s College Hospital London, Dubai, UAE; 3 Unit of Otorhinolaryngology-Head and Neck Surgery, IRCCS
Ospedale Policlinico San Martino, Genoa, Italy; 4 Department of Surgical Sciences and Integrated Diagnostic, (DISC), University
of Genoa, Genoa, Italy; 5 Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy; 6 Robert White Centre
for Airway, Voice and Swallow, Poole Hospital NHS Foundation Trust, Dorset, UK; 7 Department of Pathology, Azienda Ospedaliero-
Universitaria di Cagliari, University of Cagliari, Cagliari, Italy

SUMMARY
Objective. Bilateral selective reinnervation of the larynx aims to restore both vocal cord
tone and abductor movements in patients with bilateral vocal cord palsy.
Methods. Four females and one male treated by bilateral selective reinnervation of the lar-
ynx were included in the present study. In all cases, both posterior cricoarytenoid muscles
were reinnervated using the C3 right phrenic nerve root through the great auricular nerve
graft, while adductor muscle tone was bilaterally restored using the thyrohyoid branches of
the hypoglossal nerve through transverse cervical nerve grafts.
Results. After a minimum follow-up of 48 months, all patients were successfully tracheos-
tomy free and had recovered normal swallowing. At laryngoscopy, the first patient recov-
ered a left unilateral partial abductor movement, the second had complete bilateral abductor
movements, the third did not show improvements of abductor movements, but symptoma-
tology was improved, the fourth recovered partial bilateral abductor movements and the
fifth case did not show improvements and needed posterior cordotomy.
Conclusions. Bilateral selective laryngeal reinnervation, although a complex surgical pro-         Received: November 27, 2022
cedure, offers a more physiologic recovery in the treatment of bilateral vocal fold paralysis.     Accepted: January 14, 2023
Selection criteria still needs to be precisely defined to avoid unexpected failures.
KEY WORDS: recurrent laryngeal nerve, selective reinnervation, vocal fold paralysis,               Correspondence
                                                                                                   Filippo Carta
functional results
                                                                                                   Department of Surgery, Unit of Otorhinolaryngo-
                                                                                                   logy, Azienda Ospedaliero-Universitaria di Cagliari,
RIASSUNTO                                                                                          via Ospedale 54, 09124 Cagliari, Italy
Obiettivo. La reinnervazione bilaterale della laringe ha lo scopo di ripristinare sia il tono      E-mail: filippocarta@unica.it
delle corde vocali che i movimenti degli abduttori in pazienti con paralisi glottica bilaterale.
Metodi. Quattro donne e 1 uomo, sottoposti a reinnervazione bilaterale della laringe, sono           How to cite this article: Puxeddu R, Marrosu
stati inclusi nello studio. In tutti i casi entrambi i muscoli crico-aritenoidei posteriori sono     V, Filauro M, et al. Bilateral selective laryngeal
stati reinnervati con la radice C3 del nervo frenico. Il tono dei muscoli adduttori è stato          reinnervation in patients with bilateral vocal cord
ripristinato bilateralmente utilizzando il nervo per il muscolo tiro-ioideo, con l’interposi-        palsy. Acta Otorhinolaryngol Ital 2023;43:189-
zione di un innesto prelevato dal nervo cervicale trasverso.                                         196. https://doi.org/10.14639/0392-100X-N2395
Risultati. Dopo 48 mesi, tutti i pazienti hanno potuto chiudere il tracheostoma e recuperare
una alimentazione orale fisiologica. All’ultimo controllo fibrolaringoscopico, il primo pazien-    © Società Italiana di Otorinolaringoiatria
te ha recuperato una abduzione parziale della corda vocale sinistra, il secondo movimenti ab-      e Chirurgia Cervico-Facciale
duttori bilaterali nei limiti della norma, il terzo non ha mostrato miglioramenti della motilità
volontaria ma riferisce un miglioramento soggettivo della sintomatologia, il quarto paziente                      OPEN ACCESS
ha recuperato movimenti abduttori parziali e il quinto caso non ha avuto alcun beneficio ed è      This is an open access article distributed in accordance with
stato sottoposto a cordotomia posteriore.                                                          the CC-BY-NC-ND (Creative Commons Attribution-Non-
Conclusioni. La reinnervazione bilaterale selettiva della laringe consente un recupero di          Commercial-NoDerivatives 4.0 International) license. The
                                                                                                   article can be used by giving appropriate credit and mentio-
una funzione laringea più fisiologica in selezionati pazienti con paralisi delle corde vocali.     ning the license, but only for non-commercial purposes and
Le modalità di selezione dei pazienti devono ancora essere ben definite attraverso casisti-        only in the original version. For further information: https://
che più ampie, al fine di evitare fallimenti inattesi.                                             creativecommons.org/licenses/by-nc-nd/4.0/deed.en

PAROLE CHIAVE: nervo laringeo ricorrente, reinnervazione selettiva, paralisi delle corde
vocali, risultati funzionali
                                                                                                                                                           189
R. Puxeddu et al.




Introduction                                                     The inclusion criteria for BSLR were diagnosis of BVFP
                                                                 for more than 6 months (23, 8, 84, 12, and 96 months, re-
Bilateral vocal fold paralysis (BVFP) in adults is most
                                                                 spectively) with no sign of reinnervation of the PCA muscles
frequently observed after total thyroidectomy, due to the
                                                                 detected at pre-operative evaluation and good health status
bilateral lesion of the recurrent laryngeal nerve (RLN), al-
                                                                 (patients were fit and well, and no neuromuscular patholo-
though head and neck trauma can be a further aetiology 1-3.
                                                                 gies or respiratory diseases were present).
From 4% to 14% of patients tolerate this condition, which
                                                                 Two of 5 patients were tracheostomy dependent when re-
can be managed with conservative speech and swallowing
                                                                 ferred to our team; tracheostomy was performed at other
therapy 1,2. Botulinum toxin injections can be used in low-
                                                                 ENT departments due to acute respiratory distress.
symptomatic cases to reduce synkinesis, while gene and stem
                                                                 A multidisciplinary team was established during both pre-
cell therapy are only in the experimental phase of research 3.
                                                                 operative and post-operative work-up: neurologists, speech
When BVFP considerably compromises the airway, it rep-
                                                                 and language therapists and pneumologists were consid-
resents a dramatic and potentially life-threatening condi-
                                                                 ered necessary for the correct assessment of patients.
tion 4-6. Surgical techniques through external and endoscopic
                                                                 Pre-operative evaluations included fibrelaryngoscopy, videos-
approaches are indicated in cases of symptomatic BVFP 7.
                                                                 troboscopy, voice perceptual analysis, laryngeal electromyo-
Numerous procedures have been described and targeted to
                                                                 graphy (EMG), contrast-enhanced head and neck and chest
improve the airway without major voice disruption 8.
                                                                 computed tomography (CT), and respiratory function tests.
Usual treatments for BVFP are mainly based on a static
                                                                 In patients CA1, GE4, and GE5, pre-operative fibrelaryngos-
enlargement of the airway at the glottic level. Static glot-
                                                                 copy showed BVFP in a complete adduction position during
tic enlargement procedures consist in removal of laryngeal
                                                                 inspiration with complete glottic closure during phonation.
tissue (cordectomy plus or minus partial arytenoidectomy)
                                                                 Patient CA2 had BVFP in the paramedian position. In patient
or shifting anatomic structures (latero-fixation of the vocal
                                                                 CA3, fibrelaryngoscopy showed a near complete closure of
fold or arytenoid abduction) 7. Enlargement of the airway is
                                                                 the glottic space due to tight median position of the vocal
inevitably achieved with the worsening of voice and risk of
                                                                 folds associated with some sporadic synkinetic movements.
aspiration on swallowing.
The current challenge of treating BVFP is to restore both        Speech and language assessment consisted of the evalu-
vocal folds tone and abductor movements while preventing         ation with Grade, Roughness, Breathiness, Asthenia, and
synkinesis and swallowing impairment, without the need to        Strain (GRBAS), Voice Handicap Index (VHI) 10, Airway-
perform tissue resection 4.                                      Dyspnea-Voice-Swallow (ADVS) scales, maximum pho-
The physiological restoration of laryngeal function could        nation time (MPT), and Eating Assessment Tool (EAT) 10
be attempted with bilateral reinnervation techniques. The        scores, collected pre- and post-operatively 14-16. In the pre-
key to restoring inspiratory laryngeal abduction is to pro-      sent study, the most descriptive parameter of the GRBAS
vide an inspiratory trigger to the posterior cricoarytenoid      scale was the grade of hoarseness [G] (rating scale: 0 =
(PCA) muscles while preventing synkinetic respiratory vo-        normal; 1 = slight; 2 = moderate; 3 = severe hoarseness).
cal adduction 9.                                                 The ADVS has already been used for assessment of quality
Different methods of bilateral reinnervation of the larynx       of life in patients with BVFP 7 and evaluates four laryngeal
have been proposed in the literature, varying on the basis       functions, scoring each domain on a 1-5 scale. The EAT-10
of the donor nerves 4. In 2014, Marie reported promising         is a self-administered, symptom-specific outcome scoring
results in BVFP patients treated with bilateral selective        system for the evaluation of dysphagia 15,16. The physiologi-
laryngeal reinnervation (BSLR), reporting a decannula-           cal MPT usually ranges from 15 to 25 seconds and from 25
tion rate of 92.5% in 40 patients with more than 1 year of       to 35 seconds in women and men, respectively.
follow-up 10.                                                    Pre-operative laryngeal EMG was always performed under
To date, this BSLR technique has been reproduced in only         local anaesthesia under fibrelaryngoscopy with the ENT and
a few centers 11-13. Since these promising reports, our group    a dedicated neurophysiologist. The needle electrode posi-
performed this technique in a series of patients with BVFP       tioning must be accurate, because the insertion into adjacent
and the results are reported herein.                             pharyngeal musculature could show inspiratory muscle ac-
                                                                 tivity even in case of BVFP, producing a false positive result.
                                                                 EMG helps to objectively assess the absence of functional
Materials and methods                                            PCA movements, and to determine degrees of denervation,
Five patients (4 females, 1 male) with BVFP (identified as       spontaneous reinnervation and muscle atrophy 9.
CA1, CA2, CA3, GE4 and GE5) underwent BSLR from                  Pre-operative spirometry was performed on every patient.
October 2017 to February 2019.                                   Direct laryngoscopy under general anaesthesia was always



190
                                                                                                               Bilateral selective laryngeal reinnervation




performed before reinnervation, and bilateral crico-aryte-                  thyroid alae to visualise both RLNs and the posterior crico-
noid joint movements were evaluated to confirm that pa-                     arytenoid muscles. The RLNs were traced proximally to the
tients were not affected by ankylosis or posterior stenosis                 site of RLN injury. The distal stump of the bilateral RLNs
and, consequently, were suitable for BSLR.                                  were exposed, removing the scar tissue or neuroma. The
                                                                            postero-inferior portion of the thyroid lamina was partially
Surgical procedure                                                          removed to allow exposure of the intra-laryngeal branches
All patients underwent standard general anaesthesia and                     of the RLNs. The main trunk of the RLN was sectioned dis-
ventilation through the tracheostomy performed after intu-                  tant from the scar. The hypoglossal nerve was dissected to
bation if not already present. Laryngeal access was achieved                expose its thyrohyoid branch, easily identified using a dis-
through a horizontal neck incision made approximately                       posable nerve stimulator, and then transected as distally as
2-4 cm above the suprasternal notch at the level of the cri-                possible. The main trunk of the RLN was linked to the thy-
coid. A standard subplatysmal flap was elevated. Sterno-                    rohyoid branch of the hypoglossal nerve with interposition
cleidomastoid muscles, the anterior belly of the digastric                  of the transverse cervical nerve free graft bilaterally. The
muscles, the neurovascular bundle and the accessory nerve                   proximal end of the right phrenic nerve, sectioned after the
were bilaterally isolated. Before any further laryngeal dis-                C3 root, but before C4-C5, was anastomosed with the main
section, the great auricular nerve (GAN) and the transverse                 trunk of the Y-shaped free nerve graft, whereas each distal
cervical nerve were both isolated. A Y-shaped free nerve                    branch of the Y-shaped free nerve graft was implanted into
graft and two linear free nerve grafts were harvested for                   the main body of each PCA muscle. Neurorrhaphies were
subsequent use (Fig. 1).                                                    made using 8/0-9/0 Ethilon sutures under magnification of
Ten cm of the external jugular vein was harvested and di-                   surgical microscope. In Figure 2 a schematic representation
vided equally into 5 segments for subsequent protection of                  of the neurorrhaphies of BSLR is shown.
the nerve sutures. The right phrenic nerve was dissected                    A vein sheath segment previously harvested from the exter-
and traced retrogradely until its roots were found; its roots               nal jugular vein was used to cover each nerve suture. Finally,
(C3-C5) were identified using a disposable nerve stimula-                   the wound was closed in layers. A passive drain (Penrose)
tor, and the nerve was isolated for later use (Fig. 1).                     was used to avoid any negative pressure on the anastomoses.
Under a microscopic view (ZEISS S7 Microscope, Carl                         A cuffed tracheal tube was positioned in all patients.
Zeiss, USA; focal length 250 mm), the inferior constrictor                  Post-operative care was ward-based and did not require any
muscles were released from the posterior margins of the                     intensive care monitoring. Nevertheless, 48-hour continu-




Figure 1. Scheme of the anatomy of the nerves (drawn in yellow) used dur-   Figure 2. Schematic representation of the neurorrhaphies performed during
ing surgery for the BSLR.                                                   BSLR: donor and recipient nerves are drawn in yellow, while grafts are shown
                                                                            in green (grafts harvested from the superficial cervical plexus) and blue (the
                                                                            Y-shaped GAN graft).



                                                                                                                                                    191
R. Puxeddu et al.




ous monitoring of vital signs was performed for every pa-
tient. Antibiotics were administered daily for 7 days. Pro-
ton pump inhibitors were used to prevent gastric reflux and
potential aspiration. In addition, all patients were kept on
total parenteral nutrition for two post-operative days, and
nasogastric tube feeding was subsequently started. Pain
control was achieved using continuous morphine infusion
for the first 48 hours.
                                                                  A                                                                      B
All patients were followed-up after surgery by fibrelaryn-
goscopy. All endoscopic procedures were recorded to bet-          Figure 3. Post-operative fibrelaryngoscopy of patient CA2 showing a bilat-
ter evaluate any “new acquired movements” (NAM): the              eral Ad during phonation (A) and Ab during inspiration (B).
outcomes were codified as abduction (Ab) and adduction
(Ad). The decannulation rate and the time of decannula-           (Figs. 3A, 3B), patient CA3 did not show NAM, but her
tion were considered as parameters of surgical success in         original dyspnoea was improved; patient GE4 recovered
patients who were tracheostomised before the procedure.           bilateral Ab movements, and patient GE5 did not show any
                                                                  improvements and needed posterior cordotomy.
Results
                                                                  Functional achievements
Four patients had BVFP after thyroid surgery (cases: CA1,
                                                                  None of our patients experienced pneumonia during swal-
CA3, GE4 and GE5), and one patient (CA2) had BVFP after
                                                                  lowing training or during follow-up: the post-operative
trauma. Patient CA2 had a percutaneous gastrostomy before
                                                                  EAT 10 score was normal (score of 2 in all patients). Voice
BSLR, and two patients were tracheostomy dependent be-
                                                                  analysis showed a decreased post-operative G score in com-
fore surgery (patients CA1 and CA2). Patients CA3, GE4
                                                                  parison with pre-operative values in cases CA1, CA2 and
and GE5 underwent tracheostomy at the time of the surgical
                                                                  GE4 and remained steady in cases CA3 and GE5 (score of
procedure to avoid post-operative life-threatening complica-
                                                                  3 in both cases). The ADVS score improved in all patients.
tions. All patients underwent BSLR using the phrenic nerve
                                                                  All the patients were tracheostomy-free: the mean decan-
on the right and the thyrohyoid branch of the hypoglossal
                                                                  nulation time was 10.4 months (24, 2, 3, 8 and 15 months,
nerve bilaterally as donors. Post-operatively, four of five pa-
                                                                  respectively). Spirometry performed 12 months after sur-
tients were fed by nasogastric feeding tube, and one (CA2)
                                                                  gery showed that FVC and FEV1 were not significantly
was fed by percutaneous gastrostomy. Speech and swallow-
                                                                  different from the normal reference values in all patients:
ing therapy were started at 3 days after surgery in all cases.
                                                                  even though an overall reduction in the expiratory volumes
Nasogastric feeding tubes were removed within 7 days in           was detected due to fixed upper airway alterations in all
four patients, while patient CA2 continued feeding through        the patients, on average, a post-operative improvement was
percutaneous gastrostomy for 3 months after surgery until he      detected. Patient features and outcomes are detailed in Ta-
recovered complete oral feeding. Patients did not experience      bles I and II.
post-operative complications. Chest X-ray showed unilateral
palsy of the right diaphragm in all cases, but it was always
asymptomatic, and recovery was confirmed in all cases at          Discussion
one year after surgery.                                           Until the 1920s, tracheotomy was the only treatment that
                                                                  was routinely applied for the treatment of nonrevers-
Endoscopic findings                                               ible symptomatic BVFP. In 1922, Chevalier Jackson was
During the first months after surgery, glottic movements          the first surgeon to perform open ventriculocordectomy
were impaired and after bilateral transection of the RLN          with the intent of improving the airway while preserving
the cadaveric position reached by the vocal folds improved        the voice 17. During the seventies, arytenoidectomy by a
the airways, although tracheostomy was still needed. After        cervical approach, which was proposed by Woodman et
long-term follow-up of at least 48 months, all patients were      al. 18, obtained general agreement. Afterward, transoral
successfully tracheostomy free and recovered normal swal-         approaches were progressively developed, and currently,
lowing. At fibrelaryngoscopy/videostroboscopy, three of           transoral laser-assisted posterior cordotomy is frequently
five patients showed a “new acquired movement” (NAM):             used due to its lower complication rate, absence of an ex-
patient CA1 recovered left unilateral Ab movements, pa-           ternal scar, and shorter surgical and hospitalisation times 7.
tient CA2 recovered bilateral Ad and Ab movements                 However, airway improvement after static glottic-widening



192
                                                                                                                                   Bilateral selective laryngeal reinnervation




Table I. Pre-operative features of patients treated with selective laryngeal reinnervation for BVFP.
 Patients/sex/age            BVFP             Duration          Pre-op.          Pre-op.          Pre-op.                     Pre-op.            Pre-op.            Pre-op.
                            etiology          of BVFP             PEG         tracheostomy          ADVS                      EAT10                VHI              GIRBAS
                                                             dependence dependence
                                Thyroid
 CA1/female/44 years                             23 months              No                 Yes             4,4,2,2               13                106          3, 1, 1, 0, 1, 0
                            surgery (2015)
                                Cervical
 CA2/male/33 years                                8 months              Yes                Yes             4,4,2,5               28                110          3, 1, 1, 2, 2, 0
                             injury (2017)
                                Thyroid
 CA3/female/46 years                             84 months              No                 No              1,3,2,2               14                 22          2, 0, 2, 0, 1, 0
                            surgery (2011)
                                Thyroid
 GE4/female/59 years                             12 months              No                 No              1,4,3,2               23                 18          2, 2, 1, 1, 1, 1
                            surgery (2018)
                                Thyroid
 GE5/female/29 years                             96 months              No                 No              1,5,3,3               18                 25          3, 2, 1, 1, 1, 1
                            surgery (2010)
BVFP: bilateral vocal fold paralisis; PEG: percutaneous endoscopic gastrostomy; ADVS: airway dyspnoea voice swallowing; EAT 10: eating assessment tool; VHI: voice handicap index;
GIRBAS: grade, roughness, breathiness, asthenia, strain.



Table II. Post-operative features of patients treated with selective laryngeal reinnervation for BVFP.
 Patients                    Post-op.             Post-op.            Post-op.           Post-op.                     Post-op.             Post-op.              Post-op.
                               PEG             tracheostomy             ADVS              EAT-10                        VHI                 GRBAS               spirometry
                           dependence           dependence                                                                                                      outcomes
 CA1                                No                    No               1, 2, 2, 1               8                    80             1, 1, 0, 1, 1, 0         Improved
 CA2                                No                    No               1, 2, 2, 1               2                    35             1, 1, 0, 0, 1, 0         Improved
 CA3                                No                    No               1, 2, 2, 2               10                   15             2, 0, 2, 0, 1, 0        Unchanged
 GE4                                No                    No               1, 1, 2, 1                1                   11             1, 0, 1, 0, 0, 0         Improved
 GE5                                No                    No               1, 2, 2, 1                1                   18             3, 2, 1, 1, 1, 1        Unchanged
BVFP: bilateral vocal fold paralisis; PEG: percutaneous endoscopic gastrostomy; ADVS: airway dyspnoea voice swallowing; EAT 10: eating assessment tool; VHI: voice handicap index;
GIRBAS: grade, roughness, breathiness, asthenia, strain.



procedures is often incomplete, and is at the expense of                                   RLN has been proposed as a promising technique 9, although
poorer voice quality and increased aspiration risk 7,9.                                    very few centres have been able to reproduce the promising
Selective reinnervation of the larynx has been progressively                               results of Marie and Li 10-13 (Tab. III).
optimized to restore the function of the PCA muscles, over-
coming the limits of static glottic-widening procedures 10-13,19.                          Selection criteria
Tucker described a nerve–muscle pedicle technique using ansa                               Reinnervation procedures can be indicated when patients
hypoglossi with an island of strap muscle embedded into the                                with BVFP are fit for general anaesthesia and when the
PCA 20. He reported a 74% success rate, but deterioration was                              palsy has a traumatic aetiology with a denervation period
noticed in 17% of patients 20. Currently, the technique with                               between the onset of RLN injury and reinnervation surgery
free nerve grafting between the upper root of the right phren-                             within 18 months as suggested by Grinsell et al. 21, without
ic nerve and the bilateral PCA and between the thyrohyoid                                  a clinical history of neurologic and/or neoplastic disorders.
branch of the hypoglossal nerve and adductor branches of the                               Pre-operative laryngeal EMG is generally performed in


Table III. Literature review of patients who underwent BSLR using the phrenic nerve for the PCA and the thyrohyoid branch of the hypoglossal nerve for the ad-
ductors muscles.
 Authors                       Year                 Age            Number                                       Outcomes
                          of publication        of patients        of cases
 Lee et al. 12                   2020                  Children                 8                             100% of patients were decannulated
 Li et al. 11                    2019                   Adults                  7                              86% of patients were decannulated
 Marie et al. 10                 2014             Adults and children          49            92.5% of patients with a follow-up longer than 1 year were decannulated
 Li et al. 13                    2013                   Adults                 44                              87% of patients were decannulated




                                                                                                                                                                            193
R. Puxeddu et al.




the literature before BSLR 9,11,12,22. EMG can confirm the      Treatment
neurogenic lesions of both RLNs, shows spontaneous rein-        As described by Marie et al. 10, BSLR is based on the an-
nervation, and can exclude severe atrophy, a condition that     sa – adductor anastomoses and C3 – bilateral abductor (us-
is associated with irreversible muscular fibrotic changes       ing nerve graft) implantations 9,10. Baldissera 24 first identified
which prevent them from regaining tone and bulk with            the phrenic nerve as an ideal candidate for the reinnervation
reinnervation 9. Moreover, as reported by Song and Marie,       of the abductor muscles, and in the literature, it has been ef-
we believe that objective assessment of the absence of any      fectively associated with positive outcomes 9. Selective rein-
inspiratory PCA laryngeal EMG activity should be recom-         nervation of PCAs is achieved using a Y-shaped free nerve
mended, because, if EMG shows the presence of brisk in-         graft harvested from the GAN with the single end of the Y
spiratory activity of the PCA, the patient is not a candidate   attached to the root (usually C3) of the right phrenic nerve
for reinnervation 22.                                           (in humans, the phrenic nerve roots come from C3, C4, C5
Previous head and neck surgery could complicate the iden-       or even C6) 4. The double ends of the Y-shaped graft are di-
tification of anatomical landmarks, while the presence of       rectly implanted, one on each side, into a small pocket cre-
neoplastic lesions or neuromuscular disease preclude rein-      ated within each PCA 9. Orestes et al. 6 reported a different
nervation 9. Patients suitable for BSLR should show patho-      procedure based on the reinnervation of the PCA with the
logic VHI-10 scores and should demonstrate high demand          external branch of the superior laryngeal nerve through a
for laryngeal function restoration. An endoscopic evalua-       direct anastomosis to the distal end of the RLN, avoiding
tion under general anaesthesia is mandatory to assess the       the risk of hemidiaphragm paralysis 6. However, a significant
mobility of the cricoarytenoid joints. Failure to recognise     disadvantage of this procedure is the risk that the superior
interarytenoid scarring or cricoarytenoid joint fixation will   laryngeal nerve may not be available in patients who have
result in inappropriate patient selection and consequently      undergone thyroid surgery 3, and the abductor movement is
                                                                not triggered by the inspiratory mechanism.
poor results after BSLR 22. In cases of interarytenoid scar
                                                                According to Marie 10, the adductors are reinnervated by
or cricoarytenoid joint fixation, an endoscopic approach
                                                                transecting the main trunks of the RLNs with the aim of den-
(such as arytenoidectomy/posterior cordotomy) may be in-
                                                                ervating all the intrinsic muscles before neurorrhaphy. The
dicated 7,23.
                                                                adductors could be reinnervated with the ansa hypoglossi,
EMG obtained serially over time can detect recovery and
                                                                but more recently, the nerve for the thyrohyoid muscle has
identify neuropraxic or axonotmetic lesions 21. The lack
                                                                been identified as the best choice 9. This nerve is a branch
of spontaneous clinical or EMG recovery after three to
                                                                of the anterior cervical plexus that travels with and branch-
six months warrants reinnervation. Theoretically, there
                                                                es off the hypoglossal nerve. It is active during phonation
should be an accepted window period of 12-18 months for         and deglutition but not during respiration. It is therefore an
muscle reinnervation to be performed after the nerve in-        ideal candidate to supply laryngeal adductors, principally
jury, before irreversible motor end plate degeneration oc-      to prevent aberrant inspiratory reinnervation but perhaps
curs (chronic axotomy and muscular fibrosis), in order to       also to provide a measure of movement during phonation
achieve functional recovery 21. The effects of chronic axot-    and deglutition 9. In this way, the precise identification of
omy and muscle denervation render the tissue environment        abductor fibers of the RLN within the larynx is not neces-
suboptimal for successful axonal regeneration; as a con-        sary 9. In addition, the transection of the RLNs will create a
sequence, delays introduced by “wait-and-see” diagnos-          complete paralysis of the vocal cords, allowing for the early
tics can be costly 24, since severe atrophy, and irreversible   removal of the tracheostomy since the airways are immedi-
fibrotic changes in the muscles could prevent regain tone       ately improved with the induced cadaveric position of the
and bulk with reinnervation 9. Mackinnon 25 demonstrated        vocal cords. In our experience, although time consuming, the
that early nerve repair results in improved functional out-     nerve dissections and grafting are straightforward.
comes. Usually, 12 months are allowed for spontaneous           In our series, the post-operative palsy of the right dia-
recovery, although recent studies suggest that 6 months         phragm due to the section of the phrenic nerve was tempo-
may be enough, avoiding the risk of developing pathologic       rary and asymptomatic.
synkinetic movements 9. This delay between RLN bilateral
injury and BSLR could be unnecessary if there is clear evi-     Post-operative outcome
dence of RLN injury without any chance of spontaneous           The time of recovery is strictly related to the denervation
recovery. We believe that chronic axotomy and muscular          course. Axonal regeneration occurs from the most distal
fibrosis may have been the cause of the failure in the PCA      node of Ranvier. As many as 50-100 nodal sprouts ap-
movement recovery in CA3 and GE5.                               pear, mature into a growth cone, and elongate in response



194
                                                                                                    Bilateral selective laryngeal reinnervation




to directing signals from local tissue and denervated mo-           In the case of anatomic and functional failure of the proce-
tor receptors (neurotrophic and neurotropic factors) 21; as         dure, BSLR does not preclude the possibility of delayed or
a consequence, the interval between surgery and recovery            later laryngeal static widening surgeries, as performed in
cannot be earlier than 6 months and eventually correlated           patient GE5.
to the length of the graft.
In our series, we observed a clear correlation between a            Conclusions
shorter denervation interval time from surgery and better
outcomes: patients CA2 and GE4 were treated within one              Although it is a complex surgical procedure, BLSR offers
year after the RLN injury and experienced an initial recovery       a valid option in the treatment of BVFP. Selective reinner-
of laryngeal function within 6-8 months. Patient CA1 was            vation of the PCAs is achieved using a Y-shaped free nerve
treated 24 months after the palsy and experienced unilateral        graft harvested from the GAN with the single end of the Y
partial recovery of laryngeal motility without any pathologic       attached to the C3 root of the right phrenic, while the ad-
synkinetic movements. Patients CA3 and GE5 were treated             ductors are rightly reinnervated with the nerve to thyrohyoid
7 and 8 years after the RLN injury, respectively, and did not       muscle. The choice of the timing to perform the procedure
recover NAM. However, patient CA3 had improved symp-                is probably crucial: when reinnervation is performed within
tomatology for the reduction of pathologic synkinetic move-         one year after RLN injury, the patient has the highest chance
ments. Although our experience is limited, our failures could       of recovery, while delayed reinnervation of more than 18-
be related to a delayed reinnervation (more than 24 months          24 months is associated with a lower recovery of laryngeal
from RLN injury), as already described in other regions 21.         motility (as observed in CA3 and GE5). Although our find-
The recovery of abductor function could be related not only         ings are still limited and the technique is somewhat complex,
to the timing of the injury but also to the characteristics of      we believe that BSLR represents the first-choice option for
the grafting. Li et al. 11 reported that the free nerve graft be-   the treatment of selected patients with BVFP who request
tween the phrenic nerve and PCA should be 1 to 2 cm shorter         the attempt to restore laryngeal physiology.
in length than the free nerve graft between the thyrohyoid
branch and adductor branch of the RLN such that the regen-          Conflict of interest statement
erating axons from the different donor nerves would grow            The authors declare no conflict of interest.
into the laryngeal adductor and abductor muscles at approxi-
mately the same distance. According to Li et al. 11, another        Funding
important surgical detail is the section of the interarytenoid      This research did not receive any specific grant from fund-
branch of the RLN adductor into the larynx to prevent fibers        ing agencies in the public, commercial, or not-for-profit
from the phrenic nerve from regenerating into the laryngeal         sectors.
adductors. Furthermore, for primary nerve repair, approxi-
mately 50% of the original axons will successfully regener-         Author contributions
ate through the repair site. For a nerve graft with two sutures,    RP, KH, GPE: performed the surgeries; RP, GPE, FC, VM:
25% of axons will successfully regenerate through the graft.        designed and wrote the manuscript with support from CM,
Depending on the distance to the motor target, there will           CG, MF, FM, GPA, SMV, and MT. All the authors read and
then be additional axonal loss because of chronic axotomy           approved the final version of the manuscript.
and muscle fibrosis 24; as a consequence, the results could
be negatively affected by unpredictable and not clearly pre-        Ethical consideration
operatively identifiable definitive neuromuscular changes.          This study was approved by the Institutional Ethics Com-
The aim of BSLR for BVFP is to relieve airway compro-               mittee of our University Hospital (PG/2018/11694). The
mise, preserve voice function as much as possible and avoid         research was conducted ethically, with all study procedures
aspiration 9-11. An 8 to 10 mm glottic opening is considered        being performed in accordance with the requirements of
necessary to ensure a safe and secure airway 1. In our pa-          the World Medical Association’s Declaration of Helsinki.
tients, the main purpose to relieve airway compromise was           Written informed consent was obtained from each partici-
achieved in all cases: the two patients who were tracheos-          pant/patient for study participation and data publication.
tomy-dependent before surgery could be decannulated after
laryngeal reinnervation, while one patient who was non-tra-         References
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