CORRESPONDENCE
5. Pritchard JJ, Scott JH, Girgis FG. The structure and development of
Craniosynostosis: A Reversible
Pathology?: Comment
To the Editor: We read with interest the findings by Saljo et al1 for
their observation of new suture formation in craniosynostosis. The
authors would like to express their opinions.
There are several genetic, molecular events and deformational
forces involved in premature suture fusion development.2,3 Nor-
mally, cranial sutures constitute major bone growth sites and are
regarded as complexes of 2 osteogenic bone fronts and an inter-
vening cellular mass of undifferentiated mitotic mesenchymal cells.
These are bound by the surface of the osteogenic layer (superficial)
and the external surface of the dura mater (deep).4,5
The mouse model of craniosynostosis shows the unique and robust
capacity of suture-derived mesenchymal cells to osteogenic differ-
entiation faster than that in the patent sutures.6,7 Another theory of
craniosynostosis pathogenesis is that the reduction in the number of
suture-derived mesenchymal cells affects cranial bone quality, turn-
over, and size and is the mainstay of premature fusion.8,9 Moreover,
the osteoblast transformation rate from the central part of the bone
plate towards the suture increases rapidly in craniosynostosis leading
to bone plate hypoplasia and more osteogenic activity around the
sutures.10,11 This finding supports our clinical experience in the
distraction of craniostenotic sutures. As the hyperostosis formed in
the site of suture enables us to fix the cranial distractors in earlier ages.
Cranial expansion by distraction osteogenesis or spring treats the
symptoms not the pathology.12 In other words, the craniosynostosis
pathology is still present, which may lead to recurrent symptoms in
some patients after distraction.13,14 For this reason, the authors
propose that the patent suture in the study is a type of delayed
healing that may disappear after a long follow up period.
The radiological findings in this study are liable to bias because
healing in bones usually precedes the radiological finding.15 The
authors suggest that the only way to prove this new suture formation
is to take histopathology from it during spring removal and try to
isolate suture-derived mesenchymal cells which have unique invitro
characteristics .7,16,17
The pattern of ossification in distraction osteogenesis occurs by
intramembranous ossification.18,19 After distraction ceases, the
microcolumns of osteoid and bone grow towards each other, filling
the fibrous interzone and then lastly with remodeling of the new
bone formation.20
The most interesting finding by Salgo et al1 is the formation of a
suture shadow on the CT away from the osteotomy line and spring.
We think this should be a subject for more objective evaluation and
further research, especially on an animal model and long term
follow up of those patients with new suture formed.
Tarek Elbanoby, MD
Amr Elbatawy, MD
Al-Azhar University, Cairo, Egypt
elbanoby@azhar.edu.eg
REFERENCES
1. Säljö K, Maltese G, Tarnow P, et al. Craniosynostosis: a reversible
pathology? J Craniofac Surg 2019;30:1628–1630
2. Levi B, Wan DC, Wong VW, et al. Cranial suture biology. J Craniofac
Surg 2012;23:13–19
3. Levi B, Wan DC, Wong VW, et al. Cranial suture biology: from
pathways to patient care. J Craniofac Surg 2012;23:13–19
4. Decker JD, Hall SH. Light and electron microscopy of the new born
sagittal suture. Anat Rec 1985;212:81–89
2064 The Journal of Craniofacial Surgery  Volume 31, Number 7, October 2020
Copyright © 2020 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
cranial and facial sutures. J Anat 1956;90:73–86
6. James AW, Xu Y, Lee JK, et al. Differential effects of TGF-b1 and
TGF-b3 on chondrogenesis in posterofrontal cranial suture –
derived mesenchymal cells in vitro. Plast Reconstr Surg
2009;123:31–43
7. Xu Y, Malladi P, Chiou M, et al. Isolation and characterization of
posterofrontal/sagittal suture mesenchymal cells in vitro. Plast Reconstr
Surg 2007;119:819–829
8. Zhao H, Feng J, Ho T-V, et al. The suture provides a niche for
mesenchymal stem cells of craniofacial bones. Nat Cell Biol
2015;17:386–396
9. Flaherty K, Singh N, Richtsmeier JT. Understanding
craniosynostosis as a growth disorder. Wiley Interdiscip Rev Dev
Biol 2016;5:429–459
10. Shevde NK, Bendixen AC, Maruyama M, et al. Enhanced activity of
osteoblast differentiation factor (PEBP2(A2/CBFa1) in affected sutural
osteoblasts from patients with nonsyndromic craniosynostosis. Cleft
Palate-Craniofacial J 2001;38:606–614
11. Fragale A, Tartaglia M, Bernardini S, et al. Decreased proliferation and
altered differentiation in osteoblasts from genetically and clinically
distinct craniosynostotic disorders. Am J Pathol 1999;154:1465–1477
12. Nowinski D, Di Rocco F, Renier D, et al. Posterior cranial vault
expansion in the treatment of craniosynostosis. Comparison of
current techniques. Child’s Nerv Syst 2012;28:1537–1544
13. Foster KA, Frim DM, McKinnon M. Recurrence of synostosis following
surgical repair of craniosynostosis. Plast Reconstr Surg 2008;121:70e–
76e
14. Tahiri Y, Paliga JT, Bartlett SP, et al. New-onset craniosynostosis after
posterior vault distraction osteogenesis. J Craniofac Surg 2015;26:176–
179
15. Corrales LA, Morshed S, Bhandari M, et al. Variability in the
assessment of fracture-healing in orthopaedic trauma studies. J Bone
Joint Surg Am 2008;90:1862–1868
16. Maruyama T, Jeong J, Sheu T-J, et al. Stem cells of the suture
mesenchyme in craniofacial bone development, repair and
regeneration. Nat Commun 2016;7:1–11
17. Yu H-MI, Jerchow B, Sheu T-J, et al. The role of Axin2 in calvarial
morphogenesis and craniosynostosis. Development 2005;132:1995–
2005
18. Choi IH, Chung CY, Cho T-J, et al. Angiogenesis and mineralization
during distraction osteogenesis. J Korean Med Sci 2002;17:
435–447
19. Dornelles R, de FV, Cardim VLN, et al. Spring-mediated
skull expansion: overall effects in sutural and parasutural
areas. An experimental study in rabbits. Acta Cir Bras 2010;25:169–
175
20. Percival CJ, Richtsmeier JT. Angiogenesis and intramembranous
osteogenesis. Dev Dyn 2013;242:909–922
Vocal Fold Injury
Following Intubation
To the Editor: We read with great interest the article published in
recent issue of Journal of Craniofacial Surgery highlighting the
vocal fold injuries related to endotracheal intubation.1 It is indeed
an extremely rare but catastrophic occurrence. Endotracheal intu-
bation is one of the known etiologies of unilateral or bilateral vocal
fold immobility. The term ‘immobility’ is the preferred terminology
to be used when the vocal fold is found to be immobile without an
objective electrophysiological test result to confirm the recurrent
laryngeal nerve (RLN) state of function.
Unilateral vocal fold immobility (UVFI) can results from var-
ious primary causes. Iatrogenic injury as the most common reported
The Journal of Craniofacial Surgery  Volume 31, Number 7, October 2020
cause of UVFI and among these, thyroidectomy is the most
common surgery to post the nerve at risk.2 Other than iatrogenic
injury, non-laryngeal malignancies such as lymphoma, esopha-
geal and lung cancer as a group is also among prevalent causes
of UVFI.2 Intubation may result immobility of vocal cord either
due to mechanical cause such as in cricoarytenoid joint dis-
location or neural injury which leads to vocal fold paresis
or paralysis.
The pathophysiology of RLN injuries secondary to intubation
has been extensively investigated by many authors. In the
cadaveric dissection study, the recurrent laryngeal nerve
(RLN) is most vulnerable at approximately 6 to 8 mm below
the posterior-third of the true vocal fold, whereby the injury can
be directly from endotracheal tube (ETT) placement or by the
inflated ETT balloon.3 At this critical anatomical area, the nerve
fibers to thyroarytenoid and lateral cricoarytenoid muscles are at
most at risk as the course lies above the cricoid cartilage.4 In
comparison to nerve fibers to posterior cricoarytenoid and inter-
arytenoid muscles that lies lateral to cricoid cartilage, they are
protected from the inflated cuff pressure.4 Axonal ischemia is the
proposed pathophysiology of the RLN injury. It will results in
severe axonal injury if the intubation lasted for more than
6 hours, which subsequently causing nerve conduction failure
leading to vocal fold immobility.5
Although theoretically can happen, bilateral RLN axonal ische-
mia secondary to both side of pressure exerted from the cuffed ETT
balloon, resulting in bilateral vocal fold palsy is a real unfortunate to
occur especially in a non-neck setting surgery, which some time
may require tracheostomy to open up the airway. We have reported
one patient post thyroidectomy having bilateral vocal fold palsy
after extubation. The RLNs were functionally intact throughout the
continuous neuromonitoring intra-operatively. The condition fully
recovered after three-month, with one-week course of oral steroid at
the initial part of treatment. We postulated the fatigability of the
nerves after repeated stimulation was the underlying cause of the
bilateral transient palsy.6
The left side of vocal fold injury is more common to be reported
to be associated with intubation. The postulation is the fact that most
clinicians are right handed and thus more tendency to injure the left
side of the larynx when introducing the ETT. Second reason is the
preference of securing the ETT to right side of the patient‘s mouth
which then impose more pressure to the left side of the vocal fold
and trachea.5 The longer course of RLN on left side also imposed a
risk for compression injury over the tracheoesophageal groove.5
This laterality is the same from the surgical point of view whereby
the longer course of the left RLN has make it more susceptible to
injury from iatrogenic or sequel of a lesion etiologies.
RLN palsy commonly presents with hoarseness with variable
degree of dysphagia and aspiration symptoms. Regardless of the
cause, diminishing of the mucosal sensation and degree of glottal
gap carries risk of aspiration with subsequent increase risk of
morbidity and mortality from aspiration pneumonia. Each patient
is unique as the capability of re-innervation of the larynx is different
among individuals. However, it is suggested that any patient who is
suspected to have a new onset UVFI is referred to an otorhinolar-
yngologist for further assessment of the larynx and for immediate
intervention of UVFI to reduce the morbidity and mortality men-
tioned above.7
Norsyamira Aida Mohd Umbaik, MD
Irfan Mohamad, MD, MMed (ORL-HNS)
Department of Otorhinolaryngology–Head and Neck Surgery,
School of Medical Sciences, Universiti Sains Malaysia Health
Campus, Kota Bharu, Malaysia
irfankb@usm.my
# 2020 Mutaz B. Habal, MD
Copyright © 2020 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
Correspondence
Nik Fariza Husna Nik Hassan, MD, MMed (ORL-HNS)
Speech Pathology Programme, School of Health Sciences,
Universiti Sains Malaysia Health Campus,
Kota Bharu, Malaysia
REFERENCES
1. Evman MD, Selcuk AA. Vocal cord paralysis as a complication of
endotracheal intubation. J Craniofac Surg 2020;31:e119–e120
2. Spataro EA, Grindler DJ, Paniello RC. Etiology and time to presentation
of unilateral vocal fold paralysis. Otolaryngol Head Neck Surg
2014;151:286–293
3. Cavo JW Jr. True vocal cord paralysis following intubation.
Laryngoscope 1985;95:1352–1359
4. Goto T, Nito T, Ueha R, et al. Unilateral vocal fold adductor paralysis
after tracheal intubation. Auris Nasus Larynx 2018;45:178–181
5. Campbell BR, Shinn JR, Kimura KS, et al. Unilateral vocal fold
immobility after prolonged endotracheal intubation. JAMA
Otolaryngol Head Neck Surg 2020;146:160–167
6. Misron K, Balasubramanian A, Mohamad I, et al. Bilateral vocal cord
palsy post thyroidectomy: lessons learnt. BMJ Case Rep
2014;2014:bcr201320133
7. Lindsay R, Caitlin B, Varun A, et al. Hospitalized patients with new-onset
vocal fold immobility warrant inpatient injection laryngoplasty.
Laryngoscope [published ahead of print March 16, 2020] doi: 10.1002/
lary.28606
Clinical and Economic Impact of
The Global Smile Foundation
Surgical Program
To the Editor: Congenital clefts of the lip and palate (CLP) affect
approximately 1 in 500 to 700 live births globally, and 250,000
annually in developing countries.1 These craniofacial differences
can lead to significant patient morbidity if untreated, and can have
devastating clinical, psychosocial, and economic repercussions on
patients and their families.1 Global Smile Foundation (GSF) is a
nonprofit organization dedicated to providing free comprehensive
cleft care to patients born with CLP. The vision of GSF is to create a
world where individuals born with CLP can thrive without limita-
tions due to their craniofacial differences. GSF volunteers have
been working to achieve this vision through clinical, educational,
and research initiatives in areas of need for more than three decades.
In this report, we sought to evaluate the clinical and economic
impact of GSF’s international surgical program. GSF provides
clinical care through a diagonal model, using surgical missions
as transitory conduits for establishing more sustainable local com-
prehensive cleft care centers.1 For the analysis described here, we
reviewed all primary cleft lip (PCL) and primary cleft palate (PCP)
procedures performed over the last decade in Brazil, Burkina Faso,
Ecuador, El Salvador, Guatemala, Ivory Coast, Lebanon, Mali,
Peru, and Senegal (Fig. 1). GSF has established comprehensive cleft
care centers in Beirut, Lebanon and Guayaquil, Ecuador to date.
The total number of patients included in this study was 1509,
including 951 who underwent PCL repair, and 558 who underwent
PCP repair. The mean age of all patients was 3.3  4.3 years, 3.0  5.3
years for patients who underwent PCL repair and 3.7  2.5 years for
those who underwent PCP repair. Averted Disability-Adjusted Life
Years (DALYs) were calculated. The disability weight for untreated
cleft lips was assumed to be 0.098 with a residual disability weight of
2065