Case Reports in Neurological Medicine

Case Reports in Neurological Medicine / 2014 / Article

Case Report | Open Access

Volume 2014 |Article ID 590292 |

Michele Colaci, Giulia Cassone, Andreina Manfredi, Marco Sebastiani, Dilia Giuggioli, Clodoveo Ferri, "Neurologic Complications Associated with Sjögren’s Disease: Case Reports and Modern Pathogenic Dilemma", Case Reports in Neurological Medicine, vol. 2014, Article ID 590292, 11 pages, 2014.

Neurologic Complications Associated with Sjögren’s Disease: Case Reports and Modern Pathogenic Dilemma

Academic Editor: Jorge C. Kattah
Received26 May 2014
Revised14 Jul 2014
Accepted18 Jul 2014
Published05 Aug 2014


Objectives. Sjögren’s syndrome (SS) may be complicated by some neurological manifestations, generally sensory polyneuropathy. Furthermore, involvement of cranial nerves was described as rare complications of SS. Methods. We reported 2 cases: the first one was a 40-year-old woman who developed neuritis of the left optic nerve as presenting symptom few years before the diagnosis of SS; the second was a 54-year-old woman who presented a paralysis of the right phrenic nerve 7 years after the SS onset. An exhaustive review of the literature on patients with cranial or phrenic nerve involvements was also carried out. Results. To the best of our knowledge, our second case represents the first observation of SS-associated phrenic nerve mononeuritis, while optic neuritis represents the most frequent cranial nerve involvement detectable in this connective tissue disease. Trigeminal neuropathy is also frequently reported, whereas neuritis involving the other cranial nerves is quite rare. Conclusions. Cranial nerve injury is a harmful complication of SS, even if less commonly recorded compared to peripheral neuropathy. Neurological manifestations may precede the clinical onset of SS; therefore, in patients with apparently isolated cranial nerve involvement, a correct diagnosis of the underlying SS is often delayed or overlooked entirely; in these instances, standard clinicoserological assessment is recommendable.

1. Introduction

Sjögren’s syndrome (SS) is characterized by chronic inflammation of exocrine glands, such as lachrymal and salivary glands, leading to xerophthalmia and xerostomia [1]. Moreover, at least one third of patients present with systemic extraglandular neurological, articular, pulmonary, or gastrointestinal manifestations [2]. The prevalence of neurological manifestations in SS varies between 2% and 60%, mostly pure or predominantly sensory polyneuropathies [3]; therefore, a careful neurological evaluation is usually recommended in the global assessment of SS patients [4]. Apart from central nervous system (CNS) involvement, other neuropathic patterns are polyradiculopathies, mononeuritis multiplex, autonomic neuropathies, and cranial neuropathies [5]. These latter are not rarely observed in SS patients, often as presenting symptom in the absence of overt sicca syndrome [6, 7], thus the differential diagnosis may be quite difficult.

The pathogenic mechanisms responsible for SS neurological involvement are unknown. Many hypotheses have been considered, namely, the direct infiltration of the central nervous tissue by lymphocytic cells, the vascular injury due to antineuronal and anti-SSA antibodies, and/or the ischemia secondary to small vessel vasculitis [8].

In the present paper, we described two patients with SS, who presented mononeuritis: the first patient presented optic neuritis preceding the clinical onset of SS and the second developed a very unusual neuritis of the right phrenic nerve. Finally, a review of the literature on cervicocranial neuritis in the course of SS was carried out.

2. Case Reports

2.1. Case 1

A 40-year-old woman referred to our Rheumatology Unit in January 2012, in the suspicion of an autoimmune disorder. Since 2006, she presented episodes of left optic mononeuritis, responsive to steroids; thus, she was undergoing a neurologic follow-up for a hypothetical multiple sclerosis. The first magnetic resonance (MR) of the brain and the spine showed a solitary T2-hyperintense, gadolinium enhancing lesion of the retrobulbar and intracanalicular left optic nerve, suggestive for demyelinated plaque; anyway, the subsequent yearly MRs did not show other lesions. Since 2006, positivity for antinuclear antibodies (ANA) at the titre of 1 : 640 (speckled) was detected, along with reduced lymphocyte counts (500–600 cells/μL out of 3,500–4,000 total white cells); the screening for HCV and HBV infections was negative. Furthermore, since 2007 polyclonal hypergammaglobulinemia, slight reduction of C3 fraction of complement, and serum antitransglutaminase and anti-SSA/SSB autoantibodies were found. However, the patient did not present a clinically overt sicca syndrome; thus SS remained misdiagnosed until 2012.

Only after the patient referred to our Rheumatology Centre, a deeper check-up was performed, namely, salivary glands scintigraphy that showed mild salivary hyposecretion basally and after lemon juice stimulation and Schirmer’s test that was bilaterally positive (<5 mm). On these bases, a diagnosis of SS, classified according to the new American College of Rheumatology/Sjögren’s International Collaborative Clinical Alliance (ACR/SICCA) criteria [9], with recurrent, unilateral optic neuritis was done. Antibodies targeting aquaporin-4 (NMO antibodies) were not tested for in the serum because the test was not available; anyway, the patient did not show acute myelitis or spinal cord MRI lesions. Moreover, the possibility of optic neuritis not SS-related, but incidental only, cannot be excluded.

No chronic treatment was prescribed, except steroids in the case of the further two episodes of mild optic neuritis.

2.2. Case 2

A 54-year-old woman with diagnosis of SS-scleroderma overlap syndrome from 2005 referred to our Rheumatology Unit in January 2013. She did not present skin involvement, while an overt sicca syndrome was observed. Serum anticentromere autoantibodies were present, without anti-ENA specificity; Schirmer’s test was clearly positive (<1 mm). Videocapillaroscopy revealed an “early” scleroderma pattern; salivary glands echography evidenced a complete atrophy, while chest high-resolution computed tomography did not show interstitial lung disease, but only hypotonia of oesophagus. A labial salivary gland biopsy was not performed, since the patient refused it; thus, the diagnosis of primary SS, classified according to ACR/SICCA criteria [9], cannot be formulated.

Since 2012, the patient progressively complained of fatigue and dyspnoea in the absence of new radiological pulmonary alterations; therefore, oxygen therapy (3 L/min) was necessary. Forced vital capacity was 50% of normal value, whereas heart echography was normal. In November 2012, the diagnosis of paralysis of right diaphragm was suspected on the bases of clinical symptoms and radiological alterations at standard chest X-ray and then confirmed by the detection of mixed demyelinated/axonal damage of right phrenic nerve at electromyographic examination. A modest axonal polyneuropathy of the arms and the legs was also present, while neck MR excluded compressions of nerve roots. Treatment with steroids at 1 mg/kg/day was prescribed without significant improvement; thus the patient was referred to our Rheumatology Unit, where an immune-mediated mononeuritis of the right phrenic nerve was suspected. Therapy with monthly cycles of intravenous immunoglobulin (50 g/day, for 3 consecutive days) was decided. After the third cycle, the patient experienced reduction of dyspnoea (from 10/10 to 6/10 of modified Borg scale), improved physical performance, and tapering of daily oxygen therapy, without disease exacerbation up to date.

3. Review of the Literature

An exhaustive revision of the literature was done by including all case reports and case series of SS patients with cervical-cranial neuritis present in PubMed database (Table 1); reports regarding SS associated with other connective tissue diseases were excluded. Ninety-five reports with a total of 267 SS patients with different types of cranial neuritis during their clinical history were found [4, 7, 10101]; moreover, 68 reports with available data referred to 160 patients were analyzed in detail. In particular, the female/male ratio was 20.8, while the mean age of adult SS patients is years, consistently with recent SS epidemiological findings [102, 103]. Four cases of young girls (range 8–11 years) were also reported, all affected by optic neuritis and two by CNS involvement [34, 45, 63, 67]. Of interest, considering the 75 cases with available data, the first episode of cranial neuritis was contemporary to SS diagnosis in 40% of patients, while neuritis proceeded in 24% (range 1–35 years), or followed SS diagnosis (range 1–14 years) in 36%, respectively.

First authors/yearRef. No. pts.Age/genderOnset of neuritis versus diagnosis of SS (years)*Nerves involved/clinical featuresFollow-up

Sjogren/1935[10]1n.d.n.a.bil. VIIn.a.


Spillane/1959[12]158 F n.a.bil. V n.a.

Attwood/1961[13]150 Fn.a.III–V–VII–IXImprov. with Cs

Kaltreider/1969 [14]445 F, 48 F,
52 F, 73 F
+6; +2;
+5; +14
sV (3), bil. (pt. 3); bil. I + PNS involv. (pt. 4)1: chronic course, onset during Cs; 2, 4: Cs inefficacy; 3: response to Cs
155 F+8Iremission within 1 year

Whaley/1972[15]127 Fn.a.VResponse to Cs and P.E.

Hull/1984[16]133 F0V + PNSn.a.

Vincent/1985 [17]153 F+7V–VII–IX-diplopiaRecurrent ep. (6 in 7 years)

Alexander/1986[18]16Mean 50 Fn.a.7 II, 2 III, 1 V, 6 VI, 1 VII, 1 VIIIn.a.


Serratrice/1986[20]158 F+4VCs 20 mg/day ineffective

Malinow/1986[21]1Fn.a.V + d.r. ganglionitisn.a.


Hankey/1987[23]178 F+ (several years)V + PNS involv.n.a.

Wise/1988[24]3F− (1–6)IIn.a.

Laloux/1988[25]181 Fn.a.V + d.r. ganglionitisn.a.

Graus/1988[26]258 F, 75 Fn.a.sVn.a.

[27]128 F0MultipleResolved with Cs

Uchihara/1989[28]1n.a.n.a.bil. VIIn.a.



Flint/1990[31]1n.a.n.a.bil. sVn.a.


Semah/1990[33]157 F−11VChronic course

Berman/1990[34]110 F0II + CNS vasculitisImprov. with immunosuppressors

Berault-Dupont/1992[35]159 F0VIIImprov. to high dosage Cs

Tesar/1992[36]320 F, 35 F, 41 F0; −1; −2II, bil. III-IV–VI (pt. 1), bil. II (pt. 2), II–IX-diplopia + CNS involv. (pt. 3)Resolution with high dosage Cs (pt. 1);
improv. with high dosage Cs (pt. 2);
recurrent, resolution of neuritis with Cs/CYC within 6 months (pt. 3)


Pou Serradell/1993[38]163 F− (n.a.)III (8 ep.), multiple (5 ep.)Recurrent, responsive to Cs


Mauch/1987[40]1n.a.n.a. sVn.a.

Bakouche/1994[41]149 M− (n.a.)Diplopia-V-tinnitus Recurrent (3 ep.) solving within 3 weeks

Matsukawa/1995 [42]156 F0V then IV–VIThe first ep. autoresolved; the second with Cs

Harada/1995[43]1n.a.− (n.a.)II + acute transv. myelopathyResistant to Cs

Tajima/1997[44]9Mean 54.9 F; 51 Fn.a.8 V, 4 bil.; 1 IIn.a.

Rojas-Rodriguez/1998[45]18 F− (n.a.)IIVisual impairment not responsive to Cs, IVIG, CYC pulses

Govoni/1999[4]251 F, 24 F+6; +2VIII; III + cerebellar ataxian.a.

Dumas/1999[46]141 Fn.a. sVn.a.

Kuhl/1999[47]154 F+8IVImprov. spontaneously within few weeks

Touze/1999[48]134 F (first ep.)−35; −2; 0;
+2; + (n.a.)
VI, VII, IX, laryngeal Recurrent ep., not improv. with Cs

Oketani/1999[49]152 F+2IIImprov. to pulse Cs


Chu/2000[50]154 F0IV-VResolution with Cs and Aza within 4 weeks

Urban/2001[51]153 F+1V–IX-XChronic course

Hadithi/2001[52]141 F0VIIAutoresolution after several days


Kadota/2002[54]163 F0IIAutoresolution within 6 months

Maeda/2002[55]121 F0IIAutoresolution


Yanagihara/2002[57]139 F0IIIn.a.

Font/2003[58]6Mean 58 F−4 to 0VChronic course besides oral Cs

Delalande/2004[59]30n.a.n.a.2 I, 13 II, 5 V, 4 VII, 6 VIIIn.a.

Mori/2005[60]20Mean 55.6− (n.a.)15 V, 1 VII, 5 multiple (III, V, VI, VII, IX, X, XII)4/7 patients improv. with Cs

Rousso/2005[61]140 F0VIIRecurrent ep. that autoresolved, in 1 pt. with Cs/vit. B12 within 12 days

Oishi/2007[62]165 M0VIAutoresolved within 5 months

Cardoso/2006[63]19 F−9; 0bil. II2 ep. 9 years apart, irreversible visual loss after initial response to Cs

Galbussera/2007[64]179 F0IIIResolution with Cs and IGIV within 2 months

Pournaras/2007[65]138 M0bil. IIImprov. with Cs

Gökçay/2007[66]120 F−10IICs/Aza resistant, switch to CYC

Arabshahi/2006[67]111 F0bil. II + transv. myelitisRecurrent ep., transient improv. with Cs

Barroso/2007[68]134 F −9II + CNS involv.Recurrent ep., responsive to iv Cs

Teo/2008[69]152 F0IIIn.a.

Béjot/2008[70]153 F+ (n.a.)bil. II + aseptic meningitisImprov. with CYC

Lui/2008[71]159 M0IIIResolved with Cs/Aza within 2 weeks

Ii/2008[72]149 F0IIImprov. with IVIG




Ashraf/2009[76]147 F0V–IX–XIIResolved with Cs and MTX

Kato/2009[77]125 F+ (2)II + CNS involv.Improv. with high-dosage Cs


Kim/2009[79]7n.a.n.a.IIPoor prognosis for high relapse rate

Alhomoud/2009[80]10Mean 40 Fn.a.9 II + CNS involv.; 1 VIIn.a.

Rabadi/2010[81]123 F0IIn.a.

Sakai/2010[82]177 M0III-bil.V-VI-VIIImprov. with Cs

Imbe/2010[83]131 F0II + acute myelitisImprov. with Cs/P.E.

Nascimento/2010[84]2n.a.−10; −0.5Vn.a.

Chourkani/2010[85]243 F, 48 F0II (bil. 1 pt.)Improv. with Cs/immunosuppressors

Massara/2010[86]348, 50, 74 F+5, +6,
+16 years later
2 II, 1 VIIResolution with iv Cs

Cojocaru/2011[87]150 F+0.7; +2II then V1° ep.: improv. with Cs/IVIG; 2° ep.: Cs-resistant

Niţescu/2011[88]2n.a.+ (n.a.)IIn.a.

Yadav/2011[89]126 F+ (several years)bil. IIn.a.

Koga/2011[90]131 F0II + acute myelitisImprov. with P.E., Cs-resistant

Gono/2011[91]7Mean 44 Fn.a.3 II (1 + CNS involv.), 2 V, 1 VII, 1 IX-Xn.a.

Kolfenbach/2011[92]6n.a.n.a.IIRecurrent ep.


Horai/2012[94]863 F, 52 M, 43 F, 61 F,
51 F, 55 F, 45 F, 35 F
0 (first case); n.a.V (4 bil.)Improv. with Cs/tacrolimus (1); Improv. with Cs (1);
Improv. with symptomatic treat (3); resist. to Cs (1);
recurrent (1)

Tan/2012[95]156 F0bil. IIPermanent visual impairment

Maruta/2012[96]189 F0IIImprov. with iv Cs

Mallucci/2012[97]174 F0bil. IIn.a.

Teixeira/2013[7]4Mean 47.9 Fn.a.2 II, V, VI, 2 VII Cs almost effective

Briani/2013[98]166 F+5Vn.a.

Flanagan/2013[99]164 M0Vn.a.

Tang/2013[100]8Mean 34.7 F0IIRecurrent (3 pts), response to Cs/immunosuppressors

Present cases240 F, 54 F−6; +8II; phrenic nerveImprovement with Cs (40 F), with IVIG (54 F)

TOTAL267F/M: 20.8 Mean age: years4 I, 123 II, 8 III, 4 IV, 95 V, 17 VI, 23 VII, 9 VIII, 11 IX, 8 X, 0 XI, 6 XII ( )

(*) 0: diagnosis of SS and neuritis were contemporary; + (yrs): neuritis onset after diagnosis of SS; − (yrs): neuritis onset before diagnosis of SS. ( ) for each cranial nerve, all cases of documented involvement have been counted, even if they are included in episodes of multineuritis; therefore the total of SS patients with neuritis does not correspond to the total number of episodes with cranial nerve involvements. n.a. = not available; CNS = central nervous system; PNS = peripheral nervous system; bil. = bilateral; involv. = involvement; sV = pure sensory trigeminal involvement; d.r. ganglionitis = dorsal roots ganglionitis; transv. = transverse; ep. = episode; pt. = patient; Cs = corticosteroids; CYC = cyclophosphamide; Aza = azathioprine; IMTX = methotrexate; VIG = intravenous immunoglobulins; P.E. = plasma exchange.
3.1. Ipo-Anosmia (I Cranial Nerve)

Alterations of the I cranial nerve were rarely observed; to date, only 4 cases were described [14, 59]. However, it may be supposable that this complication is often underdiagnosed or misdiagnosed in SS patients because of the concomitant olfactory and gustatory dysfunctions secondary to mucosal dryness.

3.2. Optic Neuritis (II Cranial Nerve)

The review of the literature revealed that optic neuritis represents the 46.4% (124/267) of cranial neuritis in SS patients [7, 18, 19, 24, 34, 36, 4345, 49, 5456, 59, 63, 6568, 70, 7275, 7781, 83, 8593, 9597, 100, 104]; it is often bilateral with contemporary [65, 67, 68, 70, 85, 89, 95, 97] or sequential [36, 63] occurrence. In a few cases, neuritis was associated with CNS involvement, such as brain vasculitis [34, 77], acute transverse myelopathy [43, 67], myelitis [77, 80, 83, 90], aseptic meningitis [70], or multiple sclerosis-like features [80, 91]. Response to treatment was frequently effective, especially with the use of immunosuppressors; however, an irreversible visual impairment was occasionally reported [45, 63, 79, 95]. From a pathophysiological point of view, optic neuropathy may be related to immune-mediated small vessel vasculitis [70]; otherwise, it may be due to demyelinating disease being included or not in the neuromyelitis optica spectrum disorder [91].

The majority of published papers refer to case reports. Among cohort studies, Alexander et al. [18] investigated the presence of CNS involvement in a cohort of more than 200 SS patients, referring to the John Hopkins Medical Institute between 1980 and 1983. The 20% of these patients showed CNS complications, including 16 cases of cranial nerve involvement. In particular, 7 patients presented transient monocular optic neuritis, with new episodes of neuritis of the other eye in 5 cases. Gono et al. in 2011 [91] reported CNS complications in 56/82 SS patients, 13 of them with optic neuropathy. The spectrum of clinical features was heterogeneous, but the majority of patients presented focal or multifocal alterations preceding the diagnosis of SS. Moreover, the authors underlined that these disease complications could mimic multiple sclerosis features with possible misdiagnoses; on the other hand, they stressed the importance of screening SS patients in presence of neurologic manifestations.

3.3. Diplopia (III-IV-VI Cranial Nerves)

Diplopia is one of the most evident features related to alterations of cranial nerves, namely, oculomotor, trochlear, and abducens. Specific involvement of the III nerve in SS patients was described in 9 cases [4, 11, 18, 38, 57, 64, 69, 71], of the VI in 7 cases [18, 62], while only one patient with IV nerve alteration is present in the literature [47]. Moreover, several other reports illustrated cases of multiple neuritis including diplopia among the clinical features [7, 13, 17, 36, 41, 42, 48, 50, 60, 82]. The prognosis is generally good, with complete resolution within few weeks after steroid treatment; however, possible recurrent episodes have been reported [36, 38, 41, 48].

3.4. Trigeminal Neuropathy (V Cranial Nerve)

Trigeminal injury is the second more frequently described feature among cranial neuritis in SS patients; in fact, trigeminal neuropathy was observed in 102/267 (38%) cases, isolated or associated with other cranial nerve involvement [7, 12, 1418, 2023, 25, 26, 2933, 37, 3942, 44, 46, 50, 51, 53, 5860, 76, 82, 84, 87, 91, 94, 98, 99]. In 13 cases the neuritis was bilateral [12, 14, 31, 44, 60, 94], while in 2 it was combined to dorsal roots ganglionitis [21, 25]. The latter association may suggest a possible pathogenic mechanism of trigeminal injury that is an immune-mediated neuron death in the sensory Gasser ganglion [60]. The prominence of the sensory symptoms or the presence of several SS patients with pure sensitive trigeminal neuritis in literature may reinforce this hypothesis [14, 26, 31, 40, 46].

Considering large cohort studies, Mellgren et al. [29] retrospectively investigated the features of neural involvement in a cohort of 110 SS patients complicated by neuropathy, referred to Mayo Clinic between 1976 and 1988. Trigeminal neuropathy was recorded in 5 patients, generally associated with sensory motor polyneuropathy. In 2005, Mori et al. [60] described 92 Japanese patients with SS and neuropathy; to note, in 93% of cases the diagnosis of SS followed the onset of neural disorders. Pure sensory trigeminal neuritis affected 15 patients (6 with bilateral involvement), while 5 individuals showed multiple cranial neuropathy patterns. Overall, the prevalence of trigeminal neuropathy in SS patients seems to vary depending on ethnic factors. Anyway, the involvement of V cranial nerve in the course of SS is not rare; moreover, it tends to be recurrent or to stabilize and to be less frequently responsive to steroids than other cranial neuritis [101].

3.5. Facial Palsy (VII Cranial Nerve)

In 1935, Henrik Sjögren himself was the first author to mention cranial nerve involvement in SS patients, describing a case with bilateral facial palsy [9]; up to date, other 13 cases were described [18, 28, 35, 52, 5961, 78, 86, 91], with bilateral involvement in only one patient [28]. In other cases, facial involvement presented as multiple cranial neuritis [7, 13, 17, 48, 82], usually associated with trigeminal and/or glossopharyngeal nerve injury, generally responsive to steroid treatment.

3.6. Tinnitus (VIII Cranial Nerve)

Neuropathy of the cochlear nerve is rarely reported in the literature. Except one [41], they were described as isolated involvement [4, 18, 59]. Significant data regarding prognosis were lacking.

3.7. Involvement of IX, X, XI, and XII Cranial Nerves

A few reports described SS patients who presented difficulty of swallowing, which is a symptom of glossopharyngeal neuropathy [13, 17, 36, 48, 51, 60, 76, 91]; this nerve involvement was always reported in cases of multineuritis. Also the vagus and the hypoglossal nerves were rarely mentioned in the literature and invariably associated with the IX cranial nerve [48, 51, 60, 76, 91]. All cases seem to be related to transient, often recurrent episodes of multineuritis, generally responsive to treatment. Finally, the XI nerve involvement was never reported.

3.8. Phrenic Nerve Involvement

Phrenic nerve is not a cranial nerve; it originates in the neck from C3–C5 cervical nerves, containing motor efferent fibres to diaphragm and sensitive fibres from pericardium and visceral pleura.

The research in PubMed database of “Phrenic nerve” and “Sjögren’s syndrome” did not find any report. Furthermore, considering other autoimmune rheumatic diseases, few anecdotal reports regarding phrenic nerve involvement in systemic lupus erythematosus [105108] or ANCA-associated vasculitides [109112] were found. Up to date, diaphragm paralysis is very rarely associated with autoimmune disorders; therefore we cannot exclude that the present case number 2 represents a casual association with SS than SS-related.

4. Discussion

In the present report, two SS patients with optic and phrenic mononeuritis were described. The coexistence of a cranial neuritis in the course of SS is in keeping with the world literature reporting a number of anecdotal cases and a few cohort studies describing SS patients with cranial neuritis [4, 7, 10101]; however, to the best of our knowledge, our observation of phrenic mononeuritis represents the first patient with SS complicated by such peculiar manifestation.

Involvement of cranial nerves in SS is much less common with respect to peripheral neuropathy [91]; however, cranial neuritis may be considered relatively frequent among central nervous system neuropathic patterns (Table 2). It is not always clear whether optic neuritis, a demyelinating disease characterized by significant morbidity in more than 90% of cases [95], is secondary or coincidental with SS; anyway, both SS and optic neuritis seem to be autoimmune-driven disorder [60, 91, 93, 97]. In this respect, neuromyelitis optica (NMO), also named Devic’s disease, is a heterogeneous disease, characterized by chronic demyelinating inflammation of the optic nerve and the spinal cord, mostly characterized by the presence of antibodies targeting aquaporin-4 (NMO antibodies) with a specificity of 90% [113]; this autoantigen, expressed on astrocytes in a perivascular distribution, represents a water channel regulating the water homoeostasis in the central nervous system [114]. Initially considered as a localized form of multiple sclerosis, NMO is now classified as independent nosologic entity [115]; in 2006, modified diagnostic criteria were proposed [116], including the presence of optic neuritis, acute myelitis, and at least 2 out of the 3 following supportive criteria: contiguous spinal cord MRI lesion extending over ≥3 vertebral segments, brain MRI not meeting diagnostic criteria for multiple sclerosis, and NMO-IgG seropositive status. A few cases reported in the literature regarding SS patients with optic neuritis may be diagnosed as NMO [83, 90, 113]; indeed, many of the “SS optic neuritis” patients were described prior to the discovery of the NMO antibodies, and therefore many of these cases may actually represent NMO, and not SS-related. On the other hand, in the study by Wingerchuk et al. [104] among 71 subjects with NMO, 4 patients affected by SS were mentioned; therefore, we may assume that SS and NMO could represent comorbidity. Interestingly, the presence of NMO antibodies in SS patients has been described [75, 93, 95, 97], possibly as expression of polyclonal B cell activation typical of SS [95]; on the other hand, patients with NMO frequently have other autoantibodies of a variety of specificities, and among the commonest of these autoantibodies are SSA and SSB [74]. A comparable autoimmune mechanism against both protein sequences of aquaporin-4 (antigen specific for NMO) and aquaporin-5 (expressed in salivary glands) [113] could be hypothesized, even if evidences are still lacking. In these lights, a rheumatologic screening for latent SS is recommendable in patients with apparently isolated optic demyelinating lesions or already classified as NMO.

Cranial nerve(s)Frequency of involvement (%)Key points

I1Probably underdiagnosed because of the concomitant olfactory dysfunction secondary to mucosal dryness.

II46Possible feature of neuromyelitis optica spectrum disorder, associated with SS, otherwise, autoimmune neuritis in patients with possibly misdiagnosed SS.

III, IV, VI12Clinically evident as diplopia, this neuritis is generally responsive to steroids.

V38Autoimmune damage of the Gasser ganglion could be suspected. Neuritis tends to be recurrent or to stabilize and to be less frequently responsive to steroids than other cranial neuritis.

VII5Neuritis isolated or associated with another nerve involvement, with good prognosis.

VIII3Neuritis rarely reported as tinnitus, often isolated.

IX, X, XI, XII4Transient, often recurrent neuritis episodes, generally responsive to steroids. The IX nerve was always reported in cases of multineuritis, while the XI was never mentioned in literature.

Cranial nerves are named with their Roman numerals. The frequencies of involvement refer to the cases illustrated in Table 1, considering a total of 267 SS patients with cranial neuritis.

A pure sensory trigeminal neuropathy has been described in patients with SS [14, 26, 31, 40, 46]. Since the trigeminal sensory neurons conducing cutaneous stimuli are located in the Gasser ganglion, damage at this level is suspected. This hypothesis is supported by the study of Valls-Sole et al. [117], who carried out an electrophysiological study of the trigeminal-facial and trigeminal-trigeminal reflexes in 5 SS patients with pure sensory neuropathy, compared to subjects with sensory-motor neuropathies from other causes and to healthy controls. SS patients with pure sensory neuropathy specifically presented an abnormal blink reflex and a normal jaw jerk. These findings suggest that the damage involves the neurons of the Gasser ganglion and not the axons of the V cranial nerve.

In many cases described in literature, as well as in our patient number 1, SS was diagnosed contemporary or even after the onset of cranial neuritis. These patients are commonly referred to neurology or ophthalmology centres, where sicca syndrome or other SS manifestations, such as arthralgias and/or mild arthritis, may be underestimated or not even mentioned by the patients. Consequently, a correct diagnosis of the underlying connective tissue disease is often delayed or overlooked entirely. Nonetheless, patients with CNS involvement and/or optic neuritis may be misdiagnosed as multiple sclerosis. Thus, in patients with cranial nerve involvement it is recommendable to keep in mind the possibility of associated SS that may be easily diagnosed by standard clinicoserological assessment.

With regard to our patient number 2, the diagnosis of overlapping SS and systemic sclerosis was based on the presence of typical SS clinical manifestations, plus anticentromere autoantibodies, esophagus involvement, and scleroderma capillaroscopic pattern [118]. Yet, the typical anti-SSA/SSB autoantibodies were not found, nor a lip biopsy was carried out to ascertain the diagnosis of SS. Anyway, on the basis on the symptom complex described above, the patient might be included in the subset of patients with the so-called “ACA-positive limited scleroderma/SS overlap syndrome,” which is characterized by benign scleroderma clinical course but at a high risk of non-Hodgkin's lymphoma [119]. Interestingly, an increased frequency of peripheral neuropathy in this peculiar clinical subset has been previously reported [120]. In regard to the phrenic nerve involvement, this might represent a limited form of brachial plexopathy, in the context of a diffuse immune-mediated polyneuropathy, given the absence of brachial plexus injury at neck MR.

In conclusion, SS patients may be affected by cranial neuropathy, mainly optic neuritis or trigeminal neuropathy, which could represent the first symptom of subclinical connective tissue disease. In addition, the first observation of phrenic neuritis in a woman affected by SS and scleroderma in overlap was also described. Overall, careful clinical evaluation is recommendable in such conditions, particularly in individuals with apparently isolated cervicocranial nerve involvement.

Conflict of Interests

None of the authors have any conflict of interests to declare.


  1. A. Tincani, L. Andreoli, I. Cavazzana et al., “Novel aspects of Sjögren's syndrome in 2012,” BMC Medicine, vol. 11, no. 1, article no. 93, 2013. View at: Publisher Site | Google Scholar
  2. C. Vitali, S. Bombardieri, R. Jonsson et al., “Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group,” Annals of the Rheumatic Diseases, vol. 61, no. 6, pp. 554–558, 2002. View at: Publisher Site | Google Scholar
  3. M. García-Carrasco, M. Ramos-Casals, J. Rosas et al., “Primary Sjögren syndrome: clinical and immunologic disease patterns in a cohort of 400 patients,” Medicine, vol. 81, no. 4, pp. 270–280, 2002. View at: Publisher Site | Google Scholar
  4. M. Govoni, G. Bajocchi, N. Rizzo et al., “Neurological involvement in primary Sjogren's syndrome: clinical and instrumental evaluation in a cohort of Italian patients,” Clinical Rheumatology, vol. 18, no. 4, pp. 299–303, 1999. View at: Publisher Site | Google Scholar
  5. J. Chai and E. L. Logigian, “Neurological manifestations of primary Sjogren's syndrome,” Current Opinion in Neurology, vol. 23, no. 5, pp. 509–513, 2010. View at: Publisher Site | Google Scholar
  6. P. P. Pavlakis, H. Alexopoulos, M. L. Kosmidis et al., “Peripheral neuropathies in Sjögren's syndrome: a critical update on clinical features and pathogenetic mechanisms,” Journal of Autoimmunity, vol. 39, no. 1-2, pp. 27–33, 2012. View at: Publisher Site | Google Scholar
  7. F. D. D. Teixeira, I. Moreira, A. M. Silva, C. Vasconcelos, F. Farinha, and E. Santos, “Neurological involvement in primary sjögren's syndrome,” Acta Reumatologica Portuguesa, vol. 38, no. 1, pp. 29–36, 2013. View at: Google Scholar
  8. G. J. Tobón, J. O. Pers, V. Devauchelle-Pensec, and P. Youinou, “Neurological disorders in primary Sjogren's syndrome,” Autoimmune Diseases, vol. 2012, Article ID 645967, 11 pages, 2012. View at: Publisher Site | Google Scholar
  9. S. C. Shiboski, C. H. Shiboski, L. A. Criswell et al., “American College of rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort,” Arthritis Care & Research, vol. 64, no. 4, pp. 475–487, 2012. View at: Publisher Site | Google Scholar
  10. H. Sjogren, “Zur Kenntnis der Keratoconjunctivitis sicca.II. Allgemeine Symptomatologie und Aetiologie,” Acta Ophthalmologica, vol. 13, pp. 1–39, 1935. View at: Google Scholar
  11. F. P. Weber, “Sjögren's syndrome, especially in non-ocular features,” British Journal of Ophthalmology, vol. 29, p. 299, 1945. View at: Google Scholar
  12. J. D. Spillane and C. E. C. Wells, “Isolated trigeminal neuropathy a report of 16 cases,” Brain, vol. 82, no. 3, pp. 391–416, 1959. View at: Publisher Site | Google Scholar
  13. W. Attwood and C. M. Poser, “Neurologic complications of Sjögren's syndrome,” Neurology, vol. 11, pp. 1034–1041, 1961. View at: Publisher Site | Google Scholar
  14. H. B. Kaltreider and N. Talal, “The neuropathy of Sjögren's syndrome: trigeminal nerve involvement,” Annals of Internal Medicine, vol. 70, no. 4, pp. 751–762, 1969. View at: Publisher Site | Google Scholar
  15. K. Whaley, J. Williamson, T. Wilson et al., “Sjögren's syndrome and autoimmunity in a geriatric population,” Age and Ageing, vol. 1, no. 4, pp. 197–206, 1972. View at: Publisher Site | Google Scholar
  16. R. G. Hull, S. H. Morgan, A. E. Harding, and G. R. Hughes, “Sjögren's syndrome presenting as a severe sensory neuropathy including involvement of the trigeminal nerve,” British Journal of Rheumatology, vol. 23, pp. 301–303, 1984. View at: Google Scholar
  17. D. Vincent, P. Loron, A. Awada, and J. C. Gautier, “Recurrent multiple paralysis of cranial nerves. Gougerot-Sjögren syndrome,” Revue Neurologique, vol. 141, pp. 318–321, 1985. View at: Google Scholar
  18. E. L. Alexander, K. Malinow, and J. E. Lejewski, “Primary Sjogren's syndrome with central nervous system disease mimicking multiple sclerosis,” Annals of Internal Medicine, vol. 104, no. 3, pp. 323–330, 1986. View at: Publisher Site | Google Scholar
  19. K. Shimode, S. Kobayashi, M. Kitani, K. Okada, and T. Tsunematsu, “Optic neuritis in primary Sjogren's syndrome,” Clinical Neurology, vol. 26, no. 5, pp. 433–436, 1986. View at: Google Scholar
  20. G. Serratrice, J. Pouget, and J. C. Saint-Jean, “Sensory trigeminal neuropathy in systemic diseases: 4 cases with study of the trigeminofacial reflex,” Revue Neurologique, vol. 142, pp. 535–540, 1986. View at: Google Scholar
  21. K. Malinow, G. D. Yannakakis, S. M. Glusman et al., “Subacute sensory neuronopathy secondary to dorsal root ganglionitis in primary Sjögren's syndrome,” Annals of Neurology, vol. 20, no. 4, pp. 535–537, 1986. View at: Google Scholar
  22. E. Mauch, C. Völk, G. Kratzsch et al., “Neurological and neuropsychiatric dysfunction in primary Sjögren's syndrome,” Acta Neurologica Scandinavica, vol. 89, no. 1, pp. 31–35, 1994. View at: Google Scholar
  23. G. J. Hankey and S. S. Gubbay, “Peripheral neuropathy associated with sicca syndrome.,” Journal of Neurology Neurosurgery and Psychiatry, vol. 50, no. 8, pp. 1085–1086, 1987. View at: Publisher Site | Google Scholar
  24. C. M. Wise and C. A. Agudelo, “Optic neuropathy as an initial manifestation of Sjogren's syndrome,” The Journal of Rheumatology, vol. 15, no. 5, pp. 799–802, 1988. View at: Google Scholar
  25. P. Laloux, J. M. Brucher, J. M. Guerit, C. J. M. Sindic, and E. C. Laterre, “Subacute sensory neuronopathy associated with Sjogren's sicca syndrome,” Journal of Neurology, vol. 235, no. 6, pp. 352–354, 1988. View at: Publisher Site | Google Scholar
  26. F. Graus, A. Pou, E. Kanterewicz, and N. E. Anderson, “Sensory neuronopathy and Sjogren's syndrome: clinical and immunologic study of two patients,” Neurology, vol. 38, no. 10, pp. 1637–1639, 1988. View at: Publisher Site | Google Scholar
  27. K. Phanthumchinda, “Multiple cranial nerve palsies as a presenting symptom in primary Sjögren's syndrome.,” Journal of the Medical Association of Thailand, vol. 72, no. 5, pp. 291–294, 1989. View at: Google Scholar
  28. T. Uchihara, S. Yoshida, and H. Tsukagoshi, “Bilateral facial paresis with Sjögren's syndrome,” Journal of Neurology, vol. 236, no. 3, article 186, 1989. View at: Publisher Site | Google Scholar
  29. S. I. Mellgren, D. L. Conn, J. C. Stevens, and P. J. Dyck, “Peripheral neuropathy in primary Sjogren's syndrome,” Neurology, vol. 39, no. 3, pp. 390–394, 1989. View at: Publisher Site | Google Scholar
  30. A. P. Andonopoulos, G. Lagos, A. A. Drosos, and H. M. Moutsopoulos, “The spectrum of neurological involvement in Sjögren's syndrome,” British Journal of Rheumatology, vol. 29, pp. 21–23, 1990. View at: Publisher Site | Google Scholar
  31. S. Flint and C. Scully, “Isolated trigeminal sensory neuropathy: a heterogeneous group of disorders,” Oral Surgery, Oral Medicine, and Oral Pathology, vol. 69, no. 2, pp. 153–156, 1990. View at: Google Scholar
  32. M. Mukai, A. Sagawa, Y. Baba et al., “Neuro-psychiatric symptom associated with primary Sjögren's syndrome,” Ryumachi, vol. 30, no. 2, pp. 109–118, 1990. View at: Google Scholar
  33. F. Semah, M. Levasseur, O. Blétry, and M. G. Bousser, “Isolated trigeminal neuritis and primary Gougerot-Sjögren's syndrome,” Presse Médicale, vol. 19, article 871, 1990. View at: Google Scholar
  34. J. L. Berman, S. Kashii, M. S. Trachtman, and R. M. Burde, “Optic neuropathy and central nervous system disease secondary to Sjögren’s syndrome in a child,” Ophthalmology, vol. 97, no. 12, pp. 1606–1609, 1990. View at: Publisher Site | Google Scholar
  35. C. Berault-Dupont, H. Saveuse, H. Dechy, G. Lesur, E. Rouveix, and M. Dorra, “Peripheral facial paralysis in primary Gougerot-Sjögren primaire,” Presse Medicale, vol. 21, no. 2, pp. 83–84, 1992. View at: Google Scholar
  36. J. T. Tesar, V. M. Millan, R. Molina, and J. Armstrong, “Optic neuropathy and central nervous system disease associated with primary Sjögren’s syndrome,” American Journal of Medicine, vol. 92, no. 6, pp. 686–691, 1992. View at: Publisher Site | Google Scholar
  37. M. Soubrier, M. Vidailhet, P. Clavelou et al., “Trigeminal and connective tissue diseases,” Annales de Médecine Interne, vol. 144, pp. 379–382, 1993. View at: Google Scholar
  38. A. Pou Serradell and J. Viñas Gaya, “3 cases of rare peripheral neuropathies associated with primary Gougerot-Sjögren syndrome,” Revue Neurologique, vol. 149, no. 8-9, pp. 481–484, 1993. View at: Google Scholar
  39. I. Güell, J. Prat, O. Gaspar, and J. Alijotas, “Isolated neuropathy of the trigeminal nerve as the first manifestation of primary Sjogren syndrome,” Neurologia, vol. 8, pp. 320–321, 1993. View at: Google Scholar
  40. E. Mauch and M. Trendel, “Unilateral sensory neuropathy of the trigeminal nerve as the leading symptom of primary Sjögren syndrome (“sicca syndrome”),” Nervenarzt, vol. 58, no. 5, pp. 322–325, 1987. View at: Google Scholar
  41. P. Bakouche, J. P. Ferroir, and A. Guillard, “Multiple and recurrent paralysis of cranial nerves: primary Gougerot-Sjögren syndrome,” Revue Neurologique, vol. 150, pp. 728–731, 1994. View at: Google Scholar
  42. Y. Matsukawa, S. Nishinarita, and T. Horie, “Abducent and trochlear palsies in a patient with Sjogren's syndrome,” British Journal of Rheumatology, vol. 34, no. 5, pp. 484–485, 1995. View at: Google Scholar
  43. T. Harada, T. Ohashi, R. Miyagishi et al., “Optic neuropathy and acute transverse myelopathy in primary Sjogren's syndrome,” Japanese Journal of Ophthalmology, vol. 39, no. 2, pp. 162–165, 1995. View at: Google Scholar
  44. Y. Tajima, Y. Mito, Y. Owada et al., “Neurological manifestations of primary Sjögren's Japanese patients,” Internal Medicine, vol. 36, pp. 690–693, 1997. View at: Publisher Site | Google Scholar
  45. J. Rojas-Rodriguez, M. Garcia-Carraso, E. S. Ramirez et al., “Optic neuropathy in a child with primary Sj ögren’s syndrome,” Revue du Rhumatisme, vol. 65, pp. 355–357, 1998. View at: Google Scholar
  46. M. Dumas and R. Pérusse, “Trigeminal sensory neuropathy,” Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, vol. 87, no. 5, pp. 577–582, 1999. View at: Publisher Site | Google Scholar
  47. V. Kuhl, P. P. Urban, W. J. Mayet, and H. C. Hopf, “Isolated trochlear nerve palsy and repetitive Raynaud's phenomenon of the tongue in primary Sjogren's syndrome,” Journal of Neurology, vol. 246, no. 10, pp. 974–975, 1999. View at: Publisher Site | Google Scholar
  48. E. Touze, P. Blanche, and M. Zuber, “A 35-year history of recurrent multiple cranial neuropathy due to primary Sjogren's syndrome,” Journal of Neurology, vol. 246, no. 10, pp. 968–969, 1999. View at: Publisher Site | Google Scholar
  49. M. Oketani, H. Ideguchi, T. Ohkubo et al., “A case of Sjögren’s syndrome with retrobulbar optic neuritis and cutaneous vasculitis,” Ryumachi, vol. 39, pp. 847–852, 1999. View at: Google Scholar
  50. K. Chu, D. W. Kang, Y. W. Song, and B. W. Yoon, “Trochlear nerve palsy in Sjögren's syndrome,” Journal of the Neurological Sciences, vol. 177, pp. 157–159, 2000. View at: Google Scholar
  51. P. P. Urban, A. Keilmann, E. M. Teichmann, and H. C. Hopf, “Sensory neuropathy of the trigeminal, glossopharyngeal, and vagal nerves in Sjögren's syndrome,” Journal of the Neurological Sciences, vol. 186, no. 1-2, pp. 59–63, 2001. View at: Publisher Site | Google Scholar
  52. M. Hadithi, F. Stam, and A. J. M. Donker, “Sjögren’s syndrome: an unusual cause of Bell’s palsy,” Annals of the Rheumatic Diseases, vol. 60, pp. 724–725, 2001. View at: Google Scholar
  53. C. Lafitte, Z. Amoura, P. Cacoub et al., “Neurological complications of primary Sjögren's syndrome,” Journal of Neurology, vol. 248, no. 7, pp. 577–584, 2001. View at: Publisher Site | Google Scholar
  54. Y. Kadota, AM. Tokumaru, K. Kamakura et al., “Primary Sjögren’s syndrome initially manifested by optic neuritis: MRI findings,” Neuroradiology, vol. 44, no. 4, pp. 338–341, 2002. View at: Publisher Site | Google Scholar
  55. K. Maeda, M. Yamahira, Y. Murata, T. Uto, and H. Yasuda, “A case of retrobulbar optic neuritis associated with Sjögren syndrome which remitted spontaneously,” No To Shinkei, vol. 54, no. 11, pp. 997–1001, 2002. View at: Google Scholar
  56. J. M. Anaya, L. A. Villa, L. Restrepo, J. F. Molina, R. D. Mantilla, and S. Vargas, “Central nervous system compromise in primary Sjögren's syndrome,” Journal of Clinical Rheumatology, vol. 8, pp. 189–196, 2002. View at: Google Scholar
  57. C. Yanagihara, K. Nakaji, and Y. Nishimura, “A patient with primary Sjögren's syndrome featuring polyneuropathy and oculomotor paralysis and associated with asymptomatic left middle cerebral artery stenosis,” Rinsho Shinkeigaku, vol. 42, no. 3, pp. 216–220, 2002. View at: Google Scholar
  58. J. Font, M. Ramos-Casals, G. de la Red et al., “Pure sensory neuropathy in primary Sjögren's syndrome. Longterm prospective followup and review of the literature,” The Journal of Rheumatology, vol. 30, no. 7, pp. 1552–1557, 2003. View at: Google Scholar
  59. S. Delalande, J. de Seze, A. Fauchais et al., “Neurologic manifestations in primary Sjögren syndrome: a study of 82 patients,” Medicine, vol. 83, no. 5, pp. 280–291, 2004. View at: Publisher Site | Google Scholar
  60. K. Mori, M. Iijima, H. Koike et al., “The wide spectrum of clinical manifestations in Sjögren's syndrome-associated neuropathy,” Brain, vol. 128, pp. 2518–2534, 2005. View at: Google Scholar
  61. E. Rousso, E. Noel, J. M. Brogard, J. F. Blicklé, and E. Andrès, “Recurrent facial palsy, primary Gougerot-Sjögren's syndrome and vitamin B12 deficiency,” La Presse Médicale, vol. 34, pp. 107–108, 2005. View at: Google Scholar
  62. A. Oishi, K. Miyamoto, S. Kashii, and N. Yoshimura, “Abducens palsy and Sjögren's syndrome induced by pegylated interferon therapy,” British Journal of Ophthalmology, vol. 91, no. 6, pp. 843–844, 2007. View at: Publisher Site | Google Scholar
  63. L. M. Cardoso, L. C. Zacharias, and M. L. Monteiro, “Neuropatia òptica auto-immune: relato de caso,” Arquivos Brasileiros de Oftalmologia, vol. 69, pp. 569–593, 2006. View at: Google Scholar
  64. A. Galbussera, L. Tremolizzo, E. Tagliabue et al., “Third cranial nerve palsy? Look for a sicca syndrome,” Journal of the Neurological Sciences, vol. 253, no. 1-2, pp. 88–89, 2007. View at: Publisher Site | Google Scholar
  65. J.-A. C. Pournaras, J. D. Vaudaux, and F. Borruat, “Bilateral sequential optic neuropathy as the initial manifestation of Sjögren syndrome,” Klinische Monatsblatter fur Augenheilkunde, vol. 224, no. 4, pp. 337–339, 2007. View at: Publisher Site | Google Scholar
  66. F. Gökçay, N. Celebisoy, A. Gökçay et al., “Primary Sjögrens syndrome presenting as neuromyelitis optica,” Pediatric Neurology, vol. 36, pp. 58–60, 2007. View at: Google Scholar
  67. B. Arabshahi, A. N. Pollock, D. D. Sherry et al., “Devic disease in a child with primary Sjögren syndrome,” Journal of Child Neurology, vol. 21, pp. 285–286, 2006. View at: Google Scholar
  68. B. Barroso, “Primary Sjögren's syndrome mimicking neuromyelitis optica,” European Journal of Internal Medicine, vol. 18, no. 6, pp. 507–508, 2007. View at: Publisher Site | Google Scholar
  69. T. H. Teo, N. Yassin, C. W. Yip, and L. L. Chan, “MR findings in acute oculomotor neuropathy, leading to a diagnosis of Sjögren syndrome,” Neurology, vol. 71, no. 23, p. 1927, 2008. View at: Publisher Site | Google Scholar
  70. Y. Béjot, G. V. Osseby, D. Ben Salem et al., “Bilateral optic neuropathy revealing Sjögren's syndrome,” Revue Neurologique, vol. 164, no. 12, pp. 1044–1047, 2008. View at: Publisher Site | Google Scholar
  71. N. L. Lui, S. J. See, and J. Thumboo, “A rare cause of reversible unilateral third nerve palsy,” Journal of the Neurological Sciences, vol. 275, no. 1-2, pp. 188–190, 2008. View at: Publisher Site | Google Scholar
  72. Y. Ii, A. Shindo, R. Sasaki, Y. Naito, K. Tanaka, and S. Kuzuhara, “Reversible stenosis of large cerebral arteries in a patient with combined Sjögren's syndrome and neuromyelitis optica spectrum disorder,” Rheumatology International, vol. 28, no. 12, pp. 1277–1280, 2008. View at: Publisher Site | Google Scholar
  73. A. Javed, R. Balabanov, B. G. Arnason et al., “Minor salivary gland inflammation in Devic's disease and longitudinally extensive myelitis,” Multiple Sclerosis Journal, vol. 14, pp. 809–814, 2008. View at: Publisher Site | Google Scholar
  74. S. J. Pittock, V. A. Lennon, J. de Seze et al., “Neuromyelitis optica and non organ-specific autoimmunity,” Archives of Neurology, vol. 65, no. 1, pp. 78–83, 2008. View at: Publisher Site | Google Scholar
  75. J. H. Min, H. J. Kim, B. J. Kim et al., “Brain abnormalities in Sjogren syndrome with recurrent CNS manifestations: association with neuromyelitis optica,” Multiple Sclerosis, vol. 15, no. 9, pp. 1069–1076, 2009. View at: Publisher Site | Google Scholar
  76. V. V. Ashraf, R. Bhasi, R. P. Kumar, and A. S. Girija, “Primary Sjgren's syndrome manifesting as multiple cranial neuropathies: MRI findings,” Annals of Indian Academy of Neurology, vol. 12, no. 2, pp. 124–126, 2009. View at: Publisher Site | Google Scholar
  77. H. Kato, H. Ichikawa, D. Hayashi, T. Yamazaki, Y. Ohnaka, and M. Kawamura, “A 25-year-old woman with primary Sjögren syndrome who developed optic neuritis and encephalomyelitis associated with an anti-aquaporin 4 antibody,” Rinsho Shinkeigaku, vol. 49, no. 9, pp. 576–581, 2009. View at: Google Scholar
  78. A. Dellavance, R. R. Alvarenga, S. H. Rodrigues et al., “Anti-Aquaporin-4 antibodies are highly specific for neuromyelitis optica and show no association with Sjögren’s syndrome and other autoimmune diseases,” Arthritis & Rheumatism, vol. 60, article 503, supplement 10, 2009. View at: Google Scholar
  79. S. M. Kim, P. Waters, A. Vincent et al., “Sjögren's syndrome myelopathy: spinal cord involvement in Sjögren's syndrome might be a manifestation of neuromyelitis optica,” Multiple Sclerosis, vol. 15, no. 9, pp. 1062–1068, 2009. View at: Publisher Site | Google Scholar
  80. I. A. Alhomoud, S. A. Bohlega, M. Z. Alkawi et al., “Primary Sjogren's syndrome with central nervous system involvement,” Saudi Medical Journal, vol. 30, pp. 1067–1072, 2009. View at: Google Scholar
  81. M. H. Rabadi, S. Kundi, D. Brett, and R. Padmanabhan, “Primary Sjögren syndrome presenting as neuromyelitis optica,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 81, no. 2, pp. 213–214, 2010. View at: Publisher Site | Google Scholar
  82. K. Sakai, T. Hamaguchi, and M. Yamada, “Multiple cranial nerve enhancement on MRI in primary Sjögren's syndrome,” Internal Medicine, vol. 49, no. 9, pp. 857–859, 2010. View at: Publisher Site | Google Scholar
  83. H. Imbe, H. Nakajima, T. Ito, and H. Kitaoka, “Neuromyelitis optica in a patient with Sjögren syndrome with distal renal tubular acidosis: a case report,” Rinsho Shinkeigaku, vol. 50, no. 3, pp. 168–171, 2010. View at: Google Scholar
  84. I. S. Nascimento, E. Bonfá, J. F. de Carvalho et al., “Clues for previously undiagnosed connective tissue disease in patients with trigeminal neuralgia,” Journal of Clinical Rheumatology, vol. 16, pp. 205–208, 2010. View at: Google Scholar
  85. N. Chourkani, B. El Moutawakil, M. Sibai et al., “Primary Sjögren's syndrome and neuromyelitis optica,” La Revue de Médecine Interne, vol. 31, pp. e13–e15, 2010. View at: Google Scholar
  86. A. Massara, S. Bonazza, G. Castellino et al., “Central nervous system involvement in Sjögren's syndrome: unusual, but not unremarkable-clinical, serological characteristics and outcomes in a large cohort of Italian patients,” Rheumatology, vol. 49, no. 8, Article ID keq111, pp. 1540–1549, 2010. View at: Publisher Site | Google Scholar
  87. I. M. Cojocaru, G. Socoliuc, V. Sapira, and M. Cojocaru, “Primary Sjögren's syndrome or multiple sclerosis? Our experience concerning the dilemma of clinically isolated syndrome.,” Romanian Journal of Internal Medicine, vol. 49, no. 4, pp. 301–318, 2011. View at: Google Scholar
  88. D. Niţescu, A. Nicolau, S. Caraiola et al., “Neuromyelitis optica—complication or comorbidity in primary Sjögren's syndrome?” Romanian Journal of Internal Medicine, vol. 49, pp. 295–300, 2011. View at: Google Scholar
  89. R. Yadav, P. Krishnan, G. B. Kulkarni et al., “Spectrum of Neuro-Sjögren's syndrome a tertiary care center in south India,” Annals of Indian Academy of Neurology, vol. 14, no. 2, pp. 111–115, 2011. View at: Google Scholar
  90. S. Koga, K. Ikeda, D. Nakagomi, M. Mori, S. Kuwabara, and H. Nakajima, “A patient with neuromyelitis optica with positive anti-Ro (SS-A) antibody presenting with intractable hiccup and nausea,” Modern Rheumatology, vol. 21, no. 5, pp. 561–562, 2011. View at: Publisher Site | Google Scholar
  91. T. Gono, Y. Kawaguchi, Y. Katsumata et al., “Clinical manifestations of neurological involvement in primary Sjögren's syndrome,” Clinical Rheumatology, vol. 30, no. 4, pp. 485–490, 2011. View at: Publisher Site | Google Scholar
  92. J. R. Kolfenbach, B. J. Horner, E. D. Ferucci, and S. G. West, “Neuromyelitis optica spectrum disorder in patients with connective tissue disease and myelitis,” Arthritis Care and Research, vol. 63, no. 8, pp. 1203–1208, 2011. View at: Publisher Site | Google Scholar
  93. R. Estiasari, T. Matsushita, K. Masaki et al., “Comparison of clinical, immunological and neuroimaging features between anti-aquaporin-4 antibody-positive and antibody-negative Sjögren's syndrome patients with central nervous system manifestations,” Multiple Sclerosis, vol. 18, no. 6, pp. 807–816, 2012. View at: Publisher Site | Google Scholar
  94. Y. Horai, A. Nishino, Y. Nakashima et al., “A case of Sjögren's syndrome presenting as trigeminal nerve palsy,” Nihon Rinsho Meneki Gakkai kaishi, vol. 35, pp. 199–202, 2012. View at: Google Scholar
  95. P. Tan, W. Y. Yu, T. Umapathi, and S. Lim, “Severe optic neuritis in a patient with combined neuromyelitis optica spectrum disease and primary Sjögren's syndrome: a case report,” Journal of Medical Case Reports, vol. 6, article 401, 2012. View at: Publisher Site | Google Scholar
  96. K. Maruta, Y. Sonoda, Y. Uchida et al., “A case of neuromyelitis optica associated with anti-aquaporin 4 antibody and other autoantibodies,” Nihon Ronen Igakkai Zasshi, vol. 49, no. 4, pp. 491–495, 2012. View at: Publisher Site | Google Scholar
  97. G. Mallucci, D. Franciotta, A. Romani, M. Ceroni, and R. Bergamaschi, “Anti-aquaporin-4 antibody-positive recurrent isolated optic neuritis and primary Sjögren's syndrome,” Journal of Neurology, vol. 259, no. 8, pp. 1740–1741, 2012. View at: Publisher Site | Google Scholar
  98. C. Briani, M. Cacciavillani, and R. Gasparotti, “MRI evidence of trigeminal sensory neuropathy in Sjögren's syndrome,” Clinical Neurophysiology, vol. 124, no. 8, pp. 1703–1705, 2013. View at: Publisher Site | Google Scholar
  99. E. P. Flanagan, T. J. Kaufmann, and B. M. Keegan, “Sjögren's syndrome with trigeminal neuropathy: motor involvement,” Practical Neurology, vol. 13, no. 5, pp. 340–342, 2013. View at: Publisher Site | Google Scholar
  100. W. Q. Tang and S. H. Wei, “Primary Sjögren's syndrome related optic neuritis,” International Journal of Ophthalmology, vol. 6, pp. 888–891, 2013. View at: Google Scholar
  101. J. R. Kaplan, R. Rosenberg, E. Reinitz et al., “Invited review: peripheral neuropathy in Sjögren's syndrome,” Muscle and Nerve, vol. 13, no. 7, pp. 570–579, 1990. View at: Publisher Site | Google Scholar
  102. Y. Alamanos, N. Tsifetaki, P. V. Voulgari, A. I. Venetsanopoulou, C. Siozos, and A. A. Drosos, “Epidemiology of primary Sjögren's syndrome in north-west Greece, 1982–2003,” Rheumatology, vol. 45, no. 2, pp. 187–191, 2006. View at: Publisher Site | Google Scholar
  103. G. Westhoff and A. Zink, “Epidemiology of primary Sjörgren's syndrome,” Zeitschrift für Rheumatologie, vol. 69, pp. 41–49, 2010. View at: Google Scholar
  104. D. M. Wingerchuk, W. F. Hogancamp, P. C. O'Brien, and B. G. Weinshenker, “The clinical course of neuromyelitis optica (Devic's syndrome),” Neurology, vol. 53, no. 5, pp. 1107–1114, 1999. View at: Publisher Site | Google Scholar
  105. H. A. Al-Raqum, S. S. Uppal, M. Al-Mutairy, and R. Kumari, “Shrinking lung syndrome as a presenting manifestation of systemic lupus erythematosus in a female Kuwaiti,” Clinical Rheumatology, vol. 25, no. 3, pp. 412–414, 2006. View at: Publisher Site | Google Scholar
  106. R. Omdal, P. Roos, K. Wildhagen, and R. Gunnarsson, “Respiratory arrest in systemic lupus erythematosus due to phrenic nerve neuropathy,” Lupus, vol. 13, no. 10, pp. 817–819, 2004. View at: Publisher Site | Google Scholar
  107. W. Kössler, A. Valipour, M. Feldner-Busztin et al., “Spontaneous bilateral diaphragmatic a rare cause of respiratory failure,” Wiener klinische Wochenschrift, vol. 116, pp. 565–567, 2004. View at: Google Scholar
  108. K. Hardy, I. Herry, V. Attali et al., “Bilateral phrenic paralysis in a patient with systemic lupus erythematosus,” Chest, vol. 119, pp. 1274–1277, 2001. View at: Google Scholar
  109. K. Shimizu, H. Ohoba, H. Shimada, Y. Inoue, Y. Jinn, and N. Yoshimura, “A case of Churg-Strauss syndrome with subarachnoid hemorrhage and left phrenic nerve paralysis,” The Journal of the Japanese Respiratory Society, vol. 49, no. 9, pp. 642–646, 2011. View at: Google Scholar
  110. A. Sharma, P. Bambery, S. B. Shamanna, A. Wanchu, and S. Singh, “Phrenic nerve palsy in a patient of Churg Strauss syndrome and mononeuritis multiplex,” Clinical Rheumatology, vol. 27, no. 1, pp. 137–139, 2008. View at: Publisher Site | Google Scholar
  111. M. Armani, M. Spinazzi, C. Andrigo, A. Fassina, M. Mantovan, and B. Tavolato, “Severe dysphagia in lower cranial nerve involvement as the initial symptom of Wegener's granulomatosis,” Journal of the Neurological Sciences, vol. 263, no. 1-2, pp. 187–190, 2007. View at: Publisher Site | Google Scholar
  112. O. N. Pamuk, H. Doğutan, G. E. Pamuk, and N. Cakir, “Unilateral phrenic nerve paralysis in a patient with Wegener's granulomatosis,” Rheumatology International, vol. 23, no. 4, pp. 201–203, 2003. View at: Google Scholar
  113. J. M. Kahlenberg, “Neuromyelitis optica spectrum disorder as an initial presentation of primary Sjögren’s syndrome,” Seminars in Arthritis and Rheumatism, vol. 40, no. 4, pp. 343–348, 2011. View at: Publisher Site | Google Scholar
  114. M. A. Sahraian, E.-W. Radue, and A. Minagar, “Neuromyelitis optica : clinical manifestations and neuroimaging features,” Neurologic Clinics, vol. 31, no. 1, pp. 139–152, 2013. View at: Publisher Site | Google Scholar
  115. V. A. Lennon, D. M. Wingerchuk, T. J. Kryzer et al., “A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis,” The Lancet, vol. 364, no. 9451, pp. 2106–2112, 2004. View at: Publisher Site | Google Scholar
  116. D. M. Wingerchuk, V. A. Lennon, S. J. Pittock, C. F. Lucchinetti, and B. G. Weinshenker, “Revised diagnostic criteria for neuromyelitis optica,” Neurology, vol. 66, no. 10, pp. 1485–1489, 2006. View at: Publisher Site | Google Scholar
  117. J. Valls-Sole, F. Graus, J. Font, A. Pou, and E. S. Tolosa, “Normal proprioceptive trigeminal afferents in patients with Sjogren's syndrome and sensory neuronopathy,” Annals of Neurology, vol. 28, no. 6, pp. 786–790, 1990. View at: Publisher Site | Google Scholar
  118. C. Ferri, G. Valentini, F. Cozzi et al., “Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients,” Medicine, vol. 81, no. 2, pp. 139–153, 2002. View at: Publisher Site | Google Scholar
  119. C. Baldini, M. Mosca, A. Della Rossa et al., “Overlap of ACA-positive systemic sclerosis and Sjögren's syndrome: a distinct clinical entity with mild organ involvement but at high risk of lymphoma,” Clinical and Experimental Rheumatology, vol. 31, no. 2, pp. 272–280, 2013. View at: Google Scholar
  120. C. Salliot, L. Mouthon, M. Ardizzone, J. Sibilia, L. Guillevin, and X. Mariette, “Sjögren's syndrome is associated with and not secondary to systemic sclerosis,” Rheumatology, vol. 46, no. 2, pp. 321–326, 2007. View at: Publisher Site | Google Scholar

Copyright © 2014 Michele Colaci et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

More related articles

 PDF Download Citation Citation
 Download other formatsMore
 Order printed copiesOrder

Related articles