Involvement of multiple trigeminal nerve branches in igg4 related orbital disease

Purpose: To describe the occurrence of multiple trigeminal nerves TGNs enlargement in patients with orbital IgG4-related disease.. Ophthalmic Plast Reconstr Surg 2021;37:176–178 Enlargem

Purpose: To describe the occurrence of multiple trigeminal

nerves (TGNs) enlargement in patients with orbital

IgG4-related disease

Methods: Retrospective review of MRI findings and medical

records of 6 patients (10 orbits) with orbital IgG4-related disease

and enlargement of more than 1 TGN Orbital biopsies were

performed in all cases revealing the typical lymphoplasmacytic

infiltrate with significant plasma cell positivity for IgG4

(IgG4+/IgG ratio ≥ 40%) Three experienced neuroradiologists

reviewed the MRI sequences using a digital imaging viewer

system (Horos, https://horosproject.org/)

Results: Bilateral involvement of at least 2 TGNs divisions

was detected in all 6 patients Enlargement of both V1 and V2

nerves was diagnosed in 5 patients, and in 3 cases, all TGN

divisions were involved V2 nerves were the most affected In

this division, all 12 infraorbital nerves were enlarged, followed

by lesser palatines (10/83.3%), superior alveolar (10/83.3%),

and zygomatic (6/50%) V1 and V3 nerves were less affected

albeit 9 (75%) frontal branches (V1), and 50% of the inferior

alveolar (V3) nerves were also enlarged

Conclusions: Widespread involvement of the TGN is an

important feature of IgG4-related disease

(Ophthalmic Plast Reconstr Surg 2021;37:176–178)

Enlargement of multiple branches of the trigeminal nerves

(TGNs) is usually a sign of perineural spread of head and

neck malignancies.1 In 2011, Katsura et al.2 reported a single

patient with isolated enlargement of V2 and V3 branches who

was diagnosed as having IgG4-related inflammatory

pseudotu-mor of the TGN Following this early report, Immunoglobulin

G4-related disease (IgG4-RD) has been strongly associated with

enlargement of the infraorbital nerve (ION).3–17 The authors

de-scribe here a group of patients with IgG4-RD in whom several

branches of the TGN were enlarged

METHODS

This is a retrospective noncomparative analysis of the medi-cal records of 6 patients who presented for assessment of orbital le-sions and MRI evidence of trigeminal perineural disease The study was approved by the institutional review board of the hospital and adhered to the tenets of the Declaration of Helsinki Only patients with a biopsy-proven diagnosis of the orbital lesions and MRI imag-ing of both orbits and head were included Diagnoses were based on the histopathologic characteristics of the tissue samples and on the results of immunohistochemical staining for IgG, IgG4, CD20, CD3, CD68, S100, and CD1A

Imaging Technique Patients underwent imaging either with a Philips

Achieva 3T machine (Philips Healthcare, Best, the Netherlands) with

a 16- or 32-channel Philips head array coil, or with a 3-T scanner (Magnetom Allegra; Siemens, Erlangen, Germany) with a dedicated 32-channel head coil The imaging protocol included T1- and T2-weighted sequences on the sagittal, axial, and coronal planes of 3-mm-thick sections and no interslice gap Postcontrast T1-weighted fat-suppressed images (Magnevist; Schering, Berlin, Germany; repetition time/echo time = 400–575/13–15 milliseconds) were also obtained for all patients Additional acquisition included high-resolution 3-dimen-sional constructive interference in steady-state sequences (construc-tive interference in steady state sequence, repetition time 10.76 mil-liseconds, echo time 5.38 milmil-liseconds, 70° flip angle, 200 × 200 mm field of view, 512 × 512 mm matrix, and 64 slices

The radiologic studies of the patients were reviewed by 3 ex-perienced neuroradiologists masked to patient history, symptoms, and histopathologic data, using a digital imaging and communica-tions in Medicine viewer system (Horos, https://horosproject.org/) and Enterprise Imaging Agfa Health Care (Mortsel, Belgium) The diagno-sis of trigeminal perineural disease was based on the classic findings

of nerve enlargement or enhancement; obliteration of the fat planes around the nerves and their foramina; and enlargement and/or erosion

of foramina, canals, and fissures.18

Perineural disease was characterized according to which right- or left-sided branch of V1, V2, and/or V3 was affected Pertinent intracranial and extracranial structures (cavernous sinus, Meckel’s cave, superior orbital fissure, pterygopalatine fossa, foramen rotundum, foramen ovale, and pter-ygoid canals) and cisternal segment of TGN were also carefully assessed

RESULTS

Patients’ demographic data, diagnosis, laterality, type of orbital involvement, and clinical findings are summarized in Table 1 No pa-tient had any complaints associated with trigeminal dysfunction such as

DOI: 10.1097/IOP.0000000000001733

Accepted for publication May 5, 2020

The authors have no financial or conflicts of interest to disclose

Address correspondence and reprint requests to Antonio Augusto V Cruz,

M.D., Department of Ophthalmology, School of Medicine of Ribeirão Preto,

Hospital das Clínicas-Campus, Av Bandeirantes 900, 14049-900 Ribeirão

Preto, Brazil E-mail: aavecruz.fmrp@gmail.com

Involvement of Multiple Trigeminal Nerve Branches in

IgG4-Related Orbital Disease

Sahar M Elkhamary, M.D.*†, Antonio Augusto V Cruz, M.D.‡, Maria C Zotin, M.D.§, Murilo Cintra, M.D.§,

*Radiology Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia; †Diagnostic Radiology

Department, Mansoura Faculty of Medicine, Mansoura, Egypt; ‡Ophthalmology Department, School of Medicine of

Preto, University of São Paulo, São Paulo, Brazil; §Radiology Department, School of Medicine of

Ribeirão-Preto, University of São Paulo, São Paulo, Brazil; ‖ Department of Ophthalmology, Complejo Asistencial Palencia,

Palencia, Spain; ¶ Ophthalmology Department, Pathology Department, College of Medicine, King Saud University, Saudi Arabia; and #Pathology Department, School of Medicine of Ribeirão-Preto, University of São Paulo, São Paulo, Brazil

O riginal I nvestigation

Ophthalmic Plast Reconstr Surg, Vol 37, No 2, 2021 Trigeminal Nerve Enlargement

hypo- or hyperesthesia Orbital biopsies in all cases revealed the typical

lymphoplasmacytic infiltrate with significant plasma cell positivity for

IgG4 (IgG4+/IgG ratio ≥ 40%)

Table 2 shows the distribution of different nerve enlargement TGN

involvement was not restricted to a single TGN division in any patient

Although V2 was the most affected in all groups, at least 1 nerve of V1 or V3

was bilaterally enlarged in all patients, including those with unilateral orbital

disease Figure shows an illustrative patient (case number 5) with massive ION enlargement and bilateral involvement of V1 and V3 branches

DISCUSSION

Although it is known that TGN enlargement in IgG4-RD is not restricted to V2, the literature on this topic is limited and mainly centered on the ION In 2011, 2 articles from Japan associated

TABLE 1 Diagnoses, orbital involvement, and clinical findings

Case Sex (years) Age Laterality involvement Orbital

Clinical findings Proptosis Eye motility limitation Chemosis Conjunctival hyperemia neuropathy Optic

1 F 37 Bilateral Lacrimal gland, extraocular

muscles, apex

EOM, extraocular muscles; F, female; M, male

TABLE 2 Trigeminal branches enlarged in IgG4-RD

Patient

Orbital

involvement

AT, anterior temporal; BC, buccal; DT, deep temporal; Fr, frontal; GP, greater palatine; IA, inferior alveolar; IO, infraorbital; L, left; LC, lacrimal; LP, lesser palatine; N, nasociliary; R, right; SA, superior alveolar; Zyg, zygomatic

Multiple trigeminal nerves involvement in IgG4-RD Coronal (A) and axial slices (B) T1-weighted MRI with fat suppression and contrast

enhancement of patient no 5 Nerves (A) 1, frontal; 2, lacrimal; 3, zygomatic; 4, infraorbital; 5, inferior alveolar; and 6, posterior

supe-rior alveolar

S M Elkhamary et al Ophthalmic Plast Reconstr Surg, Vol 37, No 2, 2021

ION enlargement with IgG4-RD Watanabe et al.13 were the

first to show that ION enlargement was frequently observed in

patients with autoimmune pancreatitis, and Katsura et al.2

re-ported a patient with a mass containing abundant IgG4 + plasma

cells involving the ION, pterygopalatine fossa, and Meckel cave

The ipsilateral foramen ovale was expanded without signs of

bone destruction.2 One year later, Inoue et al.5 described lesions

involving the ION and supraorbital nerves in 5 patients with

IgG4-RD Following these early reports, several articles have

stressed the association between IgG4-related orbital disease

and ION enlargement.6,11,14–17 The authors believe that the

em-phasis on ION enlargement may simply be related to the

prox-imity of this branch to the orbital contents The nerve is easily

assessed in both CT and MRI coronal and axial slices, and it is a

natural part of the orbital imaging search pattern, while

involve-ment of other TGN branches is visualized only if a thorough

TGN examination is undertaken.18 In the authors’ patients, not

only were other V2 branches affected, but also 75% of the

su-praorbital nerves were also involved If the entire course of the

TGN is carefully studied, V1 and/or V3 branches may be found

to be abnormally enlarged

The authors are not in a position to estimate the rate of

the involvement of several trigeminal branches in IgG4-RD

be-cause only few patients with this disease have a comprehensive

MRI study of the whole TGN Although the term “perineural

spread” has been used to describe IgG4-RD enlargement of the

TGN,19 it is questionable whether this terminology is appropriate

to describe these changes Perineural spread means that specific

cells, usually malignant, have left the site of the primary lesion

and are travelling along a nerve Perineural spread is thus a form

of a metastatic disease where the tumor can disseminate along

the endoneurium or perineurium to distant areas of the body.20

The pattern of distribution of TGN enlargement associated with

IgG4-RD does not support this concept All patients with

unilat-eral orbital infiltration showed at least 1 branch enlarged on the

side contralateral to the affected orbit The authors’ case series

supports that TGN enlargement associated with IgG4-RD is a

component of the systemic disease that affects simultaneously

the orbit and the TGN and not a disease that is spreading in a

primarily contiguous fashion through the TGN

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