Peripheral nervous system involvement in systemic lupus erythematosus: Prevalence, clinical and immunological characteristics, treatment and outcome of a large cohort from a single centre.
Toledano Pilar,Orueta Ramón,Rodríguez-Pintó Ignasi,Valls-Solé Josep,Cervera Ricard,Espinosa Gerard
Disorders of peripheral nervous system in patients with systemic lupus erythematosus (PNS-SLE) are a major cause of morbidity. The aims of the present study were to determine the prevalence of PNS-SLE involvement in a large cohort of SLE patients from a single centre, to characterize such involvement, treatment modalities and outcome, and to identify the possible variables that may be associated with its presence. We performed an observational cross-sectional study that included all SLE patients being followed in our department between March and December 2015 who met at least one of the PNS-SLE case definitions proposed in 1999 by the American College of Rheumatology. Overall, 93 out of 524 (17,7%) patients presented with PNS-SLE syndrome; 90 (96.8%) of them were women with a mean age at PNS-SLE syndrome diagnosis was 44.8±14.1years and the average time from diagnosis of SLE to PNS-SLE diagnosis was 88 (range, 541-400) months. The most frequent manifestation was polyneuropathy (36.6%), followed by non-compression mononeuropathy (23.7%), cranial neuropathy and myasthenia gravis (7.5%, each), and Guillain-Barré syndrome (1.1%). The most frequent electrodiagnostic tests (EDX) pattern was axonal degeneration, present in 49 patients that corresponded to 80.3% of the overall EDX patterns. Mixed sensory-motor neuropathy was the most common type of involvement accounted for 56% of cases. Thirty-six out of 90 (40%) received glucocorticoids and/or immunosuppressant agents. Overall, global response (complete and/or partial) to treatments was achieved in 77.4% of patients without differences between the types of PNS-SLE involvement. Older age at SLE diagnosis (37.3±14.8 versus 30.8±12; p=0.001) and absence of hematologic involvement as cumulative SLE manifestation (11.8% versus 21.5%; p=0.034) had independent statistical significant associations with PNS-SLE development. The PNS-SLE involvement is not uncommon. Its most frequent manifestation is sensory-motor axonal polyneuropathy. The involvement occurs more frequently in patients who are diagnosed with SLE at older age. Prospective studies are needed to establish the incidence of PNS-SLE syndromes and the role of hematological manifestations in their development.
Patterns of peripheral neuropathy in Sjogren's syndrome in a tertiary care hospital from South India.
Sireesha Yareeda,Kanikannan Meena Angamuthu,Pyal Anjan,Sandeep Gampa,Uppin Megha S,Kandadai Rukmini Mridula,Jabeen Shaik Afshan,Varaprasad Rajendra,Rajasekhar Liza,Neeharika Mathukumalli L,Borgohain Rupam
Introduction:Sjogren's syndrome (SS) is a systemic autoimmune disease that apart from involving the exocrine glands can affect any organ. Involvement of the peripheral nervous system results in a wide spectrum of neuropathic manifestations. Objective:To evaluate the clinico-electrophysiological patterns as well as pathological characteristics of neuropathy in SS patients presenting to a neuromuscular clinic in a tertiary hospital from South India. Materials and Methods:This is a retrospective study from the Departments of Neurology, Rheumatology, and Pathology from Nizam's Institute of Medical Sciences. Twenty-one patients with the diagnosis of SS and peripheral neuropathy, seen between 2010 and 2016 were analyzed. Clinical records, conventional nerve conduction studies, and lip and nerve biopsy reports were collected. Results:Twenty one patients with SS had associated neuropathy. Female-to-male ratio was 2:1. In 14 (66.7%) patients, neuropathy was the initial manifestation, while in 4 (20%), exocrinopathy preceded neuropathy. The patterns of neuropathy included mononeuropathy multiplex (MNM) in 7 patients (30%), ganglionopathy in 4 (20%), length-dependant trigeminal autonomic neuropathy, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in 2 (10%), and cranial neuropathy in 1 (10%). Eighteen (86%) were seropositive with either anti Ro/SS-A or anti La/SS-B antibodies. Schirmer's test was positive in 13 (61.9%) patients. Nerve biopsy showed vasculitis in 5 patients and demyelinating and axonopathy in 2 patients each. Conclusions:We conclude that neuropathy is frequently the initial presentation of SS. MNM is the most common pattern followed by ganglionopathy. The pattern of neuropathy helps in arriving at the diagnosis of SS. Serology is a useful initial laboratory test. However,confirmation of SS is not by mere serology. Schirmer's test and lip biopsy are equally essential for the diagnosis, especially in seronegative patients when the clinical index of suspicion is high.
Comparison of clinical, immunological and neuroimaging features between anti-aquaporin-4 antibody-positive and antibody-negative Sjogren's syndrome patients with central nervous system manifestations.
Estiasari Riwanti,Matsushita Takuya,Masaki Katsuhisa,Akiyama Takuya,Yonekawa Tomomi,Isobe Noriko,Kira Jun-ichi
Multiple sclerosis (Houndmills, Basingstoke, England)
BACKGROUND AND OBJECTIVE:The objective of this study is to clarify clinical, immunological, and neuroimaging features in anti-aquaporin-4 (AQP4) antibody-positive and antibody-negative Sjögren's syndrome (SS) patients with central nervous system (CNS) involvement. METHODS:Medical records and MRI scans were retrospectively analyzed in 22 consecutive SS patients with CNS manifestations. RESULTS:Seven (31.8%) patients were positive for anti-AQP4 antibodies. The frequency of visual impairment was higher in anti-AQP4 antibody-positive patients than in antibody-negative patients (71.4% vs. 0.0%, p = 0.0008). Brain MRI showed that discrete lesions were more commonly found in the cerebrum, brainstem, and optic nerve in anti-AQP4 antibody-positive patients than in antibody-negative patients (p = 0.002, p = 0.006, and p = 0.004, respectively), while spinal cord MRI showed that posterior column lesions in the cervical spinal cord were more frequent in anti-AQP4 antibody-positive patients than in antibody-negative patients (71.4% vs. 14.3%, p = 0.01). SS-A antibody titers were higher in anti-AQP4 antibody-positive patients than in antibody-negative patients (p = 0.012) and were also higher in patients with longitudinally extensive spinal cord lesions (LESCLs) than in those without LESCLs (p = 0.019). CONCLUSIONS:In SS, the presence of anti-AQP4 antibodies is associated with involvement of the optic nerve, cerebrum and brainstem, and with cervical posterior column lesions in the spinal cord.
Sensory ataxic neuropathy and esophageal achalasia in a patient with Sjogren's syndrome.
Poglio Fabio,Mongini Tiziana,Cocito Dario
Muscle & nerve
We describe a patient who developed an ataxic sensory syndrome associated with xerophthalmia and progressive dysphagia with regurgitation. Electrophysiological findings were consistent with an axonal sensory neuropathy, and superficial peroneal nerve biopsy showed a reduction in number of myelinated fibers with epineurial inflammation. Rheumatoid factor, anti-SSA/SSB and antinuclear antibodies were positive and a diagnosis of Sjogren's syndrome was made. An endoscopic investigation revealed esophageal achalasia. We suggest that there may be a common autoimmune mechanism directed to different targets on the basis of this rare association.
Peripheral neuropathy and health-related quality of life in patients with primary Sjögren's syndrome: a preliminary report.
Jaskólska Marta,Chylińska Magdalena,Masiak Anna,Nowicka-Sauer Katarzyna,Siemiński Mariusz,Ziętkiewicz Marcin,Czuszyńska Zenobia,Zdrojewski Zbigniew
Sjögren's syndrome (SS) is a chronic autoimmune disease with a wide spectrum of possible organ involvement. Peripheral (PNS) and central nervous system (CNS)-related symptoms may occur in the course of the disease. The aim of this study was to compare the health-related quality of life (HR-QOL) in SS patients with and without peripheral neuropathy. The study involved 50 patients with primary Sjögren's syndrome (pSS). All patients underwent neurological clinical examination followed by nerve conduction studies (NCS) and rheumatological examination. Thirty-six-item Short Form Health Survey (SF-36) was used for evaluating HR-QOL. To assess pSS activity, the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) were used. For the assessment of clinical disability due to peripheral neuropathy, the Overall Disability Sum Score scale (ODSS) was used. Additional evaluation of pain was performed with the use of the Visual Analogue Scale (VAS) and a semistructured interview. Twenty-three (46%) patients were diagnosed with peripheral neuropathy. The most common PNS manifestation was sensorimotor neuropathy (47%). Neurological symptoms preceded the diagnosis of pSS in eight patients. The following domains of the SF-36 form were significantly lower scored by patients with peripheral nervous system involvement: role-physical [0 (0-100) vs. 75 (0-100)], role-emotional [67 (0-100) vs. 100 (0-100)], vitality [40 (10-70) vs. 50 (20-75)], bodily pain [45 (10-75) vs. 55 (0-100)], and general health [20 (5-50) vs. 30 (0-50)] (p ≤ 0.05). Our study showed that peripheral neuropathy was a common organ-specific complication in SS patients. In pSS patients, coexisting neurological involvement with symptoms such as pain and physical disability may be responsible for diminished HR-QOL.
Involvement of nervous system pathways in primary Sjögren's syndrome.
Segal Barbara,Carpenter Adam,Walk David
Rheumatic diseases clinics of North America
A wide range of central and peripheral nervous system disorders occur in patients with primary Sjögren's syndrome (pSS), although the true prevalence is an aspect which has been and remains controversial. Under-recognition of pSS and lack of consensus regarding criteria contribute to the uncertainty regarding the extent of neuropsychiatric involvement. A relatively high rate of affective and cognitive symptoms, as well as abnormal fatigue and poorly characterized pain, are features of pSS that contribute to diminishing health quality in the pSS population. This article describes the neurologic complications and controversies that surround the neurologic syndromes associated with pSS and reviews the current literature on potential immunopathogenetic mechanisms and therapy.
Acute Motor-dominant Polyneuropathy as Guillain-Barré Syndrome and Multiple Mononeuropathies in a Patient with Sjögren's Syndrome.
Tanaka Kenichiro,Nakayasu Hiroyuki,Suto Yutaka,Takahashi Shotaro,Konishi Yoshihiro,Nishimura Hirotake,Ueno Rino,Kusunoki Susumu,Nakashima Kenji
Internal medicine (Tokyo, Japan)
A patient with xerostomia and xerophthalmia due to Sjögren's syndrome presented with acute motor-dominant polyneuropathy and multiple mononeuropathy with antiganglioside antibodies. Nerve conduction studies and a sural nerve biopsy revealed the neuropathy as a mixture of segmental demyelination and axonal degeneration. Positive results were obtained for several antiganglioside antibodies. Corticosteroid treatment proved effective. The neuropathy was considered to represent a mixture of polyneuropathy as Guillain-Barré syndrome and multiple mononeuropathy via Sjögren's syndrome. We speculate that Guillain-Barré syndrome occurred in the patient and Guillain-Barré syndrome itself activated multiple mononeuropathy via Sjögren's syndrome.
Posterior reversible encephalopathy syndrome as an initial neurological manifestation of primary Sjögren's syndrome.
Jeong Ha-Neul,Suh Bum Chun,Kim Yong Bum,Chung Pil-Wook,Moon Heui-Soo,Yoon Won Tae
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
It is well known that patients with peripheral neuropathy along with autonomic involvement can also exhibit autonomic hyperactivity. There are rare cases in which these patients developed posterior reversible encephalopathy syndrome (PRES). Patients with primary Sjögren's syndrome (pSS) may be more likely to exhibit autonomic hypofunction rather than autonomic hyperfunction, which is a rare event. In the present work, we report the first known case of PRES as an initial neurological manifestation of pSS.
Biopsy-Proven Small-Fiber Neuropathy in Primary Sjögren's Syndrome: Neuropathic Pain Characteristics, Autoantibody Findings, and Histopathologic Features.
Birnbaum Julius,Lalji Aliya,Saed Aveen,Baer Alan N
Arthritis care & research
OBJECTIVE:Painful small-fiber neuropathies (SFNs) in primary Sjögren's syndrome (SS) may present as pure or mixed with concurrent large-fiber involvement. SFN can be diagnosed by punch skin biopsy results that identify decreased intra-epidermal nerve-fiber density (IENFD) of unmyelinated nerves. METHODS:We compared 23 consecutively evaluated patients with SS with pure and mixed SFN versus 98 patients without SFN. We distinguished between markers of dorsal root ganglia (DRG) degeneration (decreased IENFD in the proximal thigh versus the distal leg) versus axonal degeneration (decreased IENFD in the distal leg versus the proximal thigh). RESULTS:There were no differences in pain intensity, pain quality, and treatment characteristics in the comparison of 13 patients with pure SFN versus 10 patients with mixed SFN. Ten patients with SFN (approximately 45%) had neuropathic pain preceding sicca symptoms. Opioid analgesics were prescribed to approximately 45% of patients with SFN. When compared to 98 patients without SFN, the 23 patients with SFN had an increased frequency of male sex (30% versus 9%; P < 0.01), a decreased frequency of anti-Ro 52 (P = 0.01) and anti-Ro 60 antibodies (P = 0.01), rheumatoid factor positivity (P < 0.01), and polyclonal gammopathy (P < 0.01). Eleven patients had stocking-and-glove pain, and 12 patients had nonstocking-and-glove pain. Skin biopsy results disclosed patterns of axonal (16 patients) and DRG injury (7 patients). CONCLUSION:SS SFN had an increased frequency among male patients, a decreased frequency of multiple antibodies, frequent treatment with opioid analgesics, and the presence of nonstocking-and-glove pain. Distinguishing between DRG versus axonal injury is significant, especially given that mechanisms targeting the DRG may result in irreversible neuronal cell death. Altogether, these findings highlight clinical, autoantibody, and pathologic features that can help to define mechanisms and treatment strategies.
Diagnostic and prognostic relevance of neuromuscular biopsy in primary Sjögren's syndrome-related neuropathy.
Terrier Benjamin,Lacroix Catherine,Guillevin Loïc,Hatron Pierre-Yves,Dhote Robin,Maillot François,Diot Elisabeth,Sarrot-Reynauld Françoise,Sordet Christelle,Dubourg Odile,Meyer Laurence,Mariette Xavier,Gottenberg Jacques-Eric,
Arthritis and rheumatism
OBJECTIVE:To evaluate the clinicobiologic presentation in patients with primary Sjögren's syndrome (SS)-related peripheral neuropathy, the histologic results of neuromuscular biopsy (NMB), and clinical outcome, and to identify prognostic factors. METHODS:We retrospectively studied clinical and biologic presentation of 40 patients with primary SS-related neuropathy who underwent NMB. Prognostic factors of clinical outcome were assessed by univariate and multivariate analysis. RESULTS:Patients with vasculitis (lymphocytic [n = 8] or necrotizing [n = 14]) had a higher prevalence of acute-onset neuropathy, multiple mononeuropathy, sensorimotor involvement, vascular purpura, general symptoms, increased C-reactive protein level, positivity for rheumatoid factor, hypocomplementemia, and monoclonal gammopathy compared with those without vasculitis (n = 18). Comparison between patients with necrotizing or lymphocytic vasculitis did not reveal significant differences in clinical or biologic presentation except for the presence of general symptoms and rheumatoid factor. Regarding clinical evolution, the results of NMB (P < 0.0001), in particular the presence of necrotizing vasculitis (P < 0.001), an acute neuropathy onset (P < 0.0001), general symptoms (P < 0.0001), multiple mononeuropathy (P = 0.0007), presence of sensorimotor involvement (P = 0.002), and increased C-reactive protein level (P = 0.008), were significantly associated with a better outcome in univariate analysis. In multivariate analysis, NMB resulting in the identification of patients with necrotizing vasculitis was the only variable that remained significantly associated with a better outcome (P = 0.01). CONCLUSION:NMB is necessary to identify patients with necrotizing vasculitis, who have a better response to immunosuppressive therapy. NMB might therefore have both a diagnostic and prognostic relevance in primary SS-related neuropathy.
[The neurological manifestations in 52 patients with primary Sjögren's syndrome].
Zhang Y,Xu Y,Zhao J L,Li M T,Zhao Y,Zeng X F,Cui L Y
Zhonghua nei ke za zhi
To summarize the neurological manifestations in patients with primary Sjögren's syndrome (pSS). A total of 68 patients were diagnosed as pSS in neurology department of Peking Union Medical College Hospital from March 2014 to February 2018, among whom sixteen cases were excluded due to modified final diagnoses of primary neurological diseases. Therefore 52 pSS patients with neurological involvement were enrolled and retrospectively analyzed. They were divided into two groups as extensive group in which both central and peripheral nervous system were involved, non-extensive group in which either central or peripheral nervous system was involved. Neurological manifestations were presented as primary symptoms in 98.1%(51/52) patients, while 35 had neurological involvement as their only extraglandular manifestations. Thirteen cases were in extensive group. The other 39 in non-extensive group including 22 cases with only peripheral nervous system involved and 17 cases with only single central nervous system involved. Compared to non-extensive group, the proportion of woman patients [13/13 vs.71.8% (28/39), =0.047], serum IgG level [17.73(11.11,22.41)g/L vs. 11.49(9.58,13.40)g/L, =0.017] and positive rates of oligoclonal band (OB) in cerebral spinal fluid (CSF) [7/13 vs. 22.6%(7/31), =0.042)] were significantly higher in extensive involvement group. Neurological manifestations in pSS patients could be extensive, both central and peripheral nervous system might be associated. Female patients, high serum IgG level and positive OB in CSF are risk factors of extensive neurological involvement, suggesting that the immune system may be generally over-stimulated.
Immunosuppressive treatment for peripheral neuropathies in Sjogren's syndrome - a systematic review.
Humă Andreea Camelia,Kecskeş Evelyn Maria,Tulbă Delia,Bălănescu Paul,Băicuş Cristian
Romanian journal of internal medicine = Revue roumaine de medecine interne
BACKGROUND:Sjogren's syndrome (SS) is among the most frequent autoimmune diseases and one of its most severe extraglandular manifestations is peripheral neuropathy. There is no consensus about peripheral neuropathy treatment in SS. Our aim is to identify studies proving the efficiency of immunosuppressive treatment on peripheral neuropathies in SS. METHODS:The search was conducted on the PubMed (MEDLINE) database. Studies with patients diagnosed with SS and peripheral neuropathy were included. Treatment with one of the following was among inclusion criteria: glucocorticoids (GC), rituximab (RTX), azathioprine (AZA), mycophenolic acid (MMF), cyclophosphamide (CP), methotrexate (MTX), plasmapheresis or iv immunoglobulins (IV IG). RESULTS:A total of 116 results were found and abstracts were examined. 103 papers were excluded, and the remaining 13 papers were analyzed. They were 3 case series and 10 case reports, retrospective, totalizing 62 patients of which 22 (35.5%) received IV IG, 8 (13%) received RTX, 7 (11%) CP, and 5 (8%) received only GC. Drug associations containing corticosteroids were frequent. Of those 22 treated with IV IG, 18 patients improved (82%), and 4 stabilized (18%). IV IG was useful in sensory, motor and sensorimotor neuropathies. CP had good results in mononeuritis multiplex, while autonomic neuropathies responded well to GC or RTX. AZA, RTX, MTX, MMF or plasmapheresis were not used alone. Follow-up periods were heterogenous and the evaluation of the neuropathy was not systematic. CONCLUSION:There is only low level evidence (retrospective case reports and case series). In most cases, IV IG treatment in patients with peripheral neuropathies and SS resulted in clinical improvement, while other therapies, such as RTX, corticosteroids and CP proved to be useful in a handful of cases.
The kaleidoscope of neurological manifestations in primary Sjögren's syndrome.
Alunno Alessia,Carubbi Francesco,Bartoloni Elena,Cipriani Paola,Giacomelli Roberto,Gerli Roberto
Clinical and experimental rheumatology
Neurologic involvement is a common extraglandular manifestation of primary Sjögren's syndrome (pSS), is varied and can be divided anatomically into 3 categories: central nervous system, peripheral neuropathies and autonomous nervous system manifestations. According to different study cohorts, neurological manifestations can occur in 18-45% of pSS patients, with the peripheral nervous system being the most frequent site of involvement compared to the central nervous system and autonomic system. Some neurologic complications share convergent pathophysiology, although the pathological basis of other conditions, namely cognitive impairment in pSS, is less clear. The heterogeneity of neurologic manifestations in pSS complicates the diagnosis and approach to treatment, which should be directed toward the underlying neuro-pathologic mechanism. The diagnosis and treatment of these manifestations must be optimised in order to avoid severe disability. However, for the majority of the complications, evidence for treatment efficacy is limited and requires further investigation.
Efficacy of rituximab in primary Sjogren's syndrome with peripheral nervous system involvement: results from the AIR registry.
Mekinian A,Ravaud P,Hatron P Y,Larroche C,Leone J,Gombert B,Hamidou M,Cantagrel A,Marcelli C,Rist S,Breban M,Launay D,Fain O,Gottenberg J E,Mariette X
Annals of the rheumatic diseases
OBJECTIVE:To evaluate rituximab (RTX) in primary Sjögren's syndrome (pSS) with peripheral nervous system (PNS) involvement. METHODS:Patients with pSS and PNS involvement who were included in the French AIR registry were analysed. RESULTS:17 patients (age 60 years (44-78 years); 14 were female) were analysed. Neurological improvement was noted in 11 patients (65%) at 3 months. Rankin scale decreased from 3 (1-5) to 2 (1-5), 2 (1-5) and 2 (1-6) after 3, 6 and 9 months (p=0.02). European Sjögren's Syndrome Disease Activity Index decreased from 18 (10-44) to 11 (5-20), 11 (5-29) and 12 (5-30) after 3, 6 and 9 months (p<0.05). RTX was effective in neurological involvement in 9/10 patients with vasculitis or cryoglobulinaemia (90%) (group 1) at 3 months and in 2/7 cases (29%) without cryoglobulinaemia and vasculitis (p=0.03). Rankin and European Sjögren's Syndrome Disease Activity Index scales decreased significantly in group 1. CONCLUSION:RTX seems effective in cryoglobulinaemia or vasculitis-related PNS involvement in pSS.
Is there specific neurological disorders of primary Sjögren's syndrome?
Carvajal Alegria Guillermo,Guellec Dewi,Devauchelle-Pensec Valérie,Saraux Alain
Joint bone spine
Neurological manifestations of primary Sjögren's syndrome are multiple and appear frequently. Depending on data analysis, patient recruitment, and diagnosis criteria used to defined primary Sjögren's syndrome or neurological manifestations, the estimated prevalence is between 0 and 70%. Peripheral neurological complications seem the most common, particularly sensory-motors axonal neuropathies. Neuronopathy seems to be the most specific neurological complication of primary Sjögren's syndrome. Central manifestations of primary Sjögren's syndrome are not uncommon, but the neurological complication's spectrum is not well defined. Neuromyelitis optica is regularly found among central complications. To conclude, although central and peripheral complications of primary Sjögren's syndrome are difficult to assess, partly because of the wide spectrum of possible manifestations, it is around 20%. Neuronopathy is still the most specific complication.
Neurological manifestations of primary Sjogren's syndrome.
Chai Josiah,Logigian Eric L
Current opinion in neurology
PURPOSE OF REVIEW:This review summarizes our current understanding of the neurological manifestations of primary Sjogren's syndrome (PSS), their pathophysiology, and treatment. RECENT FINDINGS:Prevalence of neurological manifestations in PSS varies widely from 10 to 60%, with pure or predominantly sensory polyneuropathies as the most common neurologic manifestation (e.g. sensory ataxic or small fiber sensory painful neuropathy). Mononeuropathy multiplex, polyradiculopathy, symptomatic dysautonomia, cranial neuropathy, myopathy, and central nervous system involvement are less common. PSS-associated sensory neuropathy is often the presenting feature of Sjogren's syndrome and, therefore, a high index of suspicion is required, particularly in female patients with nonlength-dependent, painful, or ataxic sensory neuropathies or those with trigeminal sensory and autonomic involvement. The pathophysiological basis of PSS-associated neuropathy is still unclear. Dorsal root ganglionitis and peripheral nerve vasculitis have been observed on histological examination of biopsy and autopsy samples. A few studies have explored the fundamental role of humoral autoimmune mechanisms. Small, uncontrolled, treatment trials with numerous immunomodulatory agents have reported variable benefit in PSS-associated neuropathy, particularly corticosteroids for mononeuritis multiplex and intravenous immunoglobulin for small fiber or sensory ataxic neuropathy. SUMMARY:The clinical and histological spectrum of neurological manifestations of Sjogren's syndrome is becoming clear. The field needs further exploration of basic neuroimmunological mechanisms of neural injury, and controlled treatment trials.
Relation of sensory peripheral neuropathy in Sjögren syndrome to anti-Ro/SSA.
Scofield Amanda Kyle,Radfar Lida,Ice John A,Vista Evan,Anaya Juan-Manuel,Houston Glen,Lewis David,Stone Donald U,Chodosh James,Hefner Kimberly,Lessard Christopher J,Moser Kathy L,Scofield Robert Hal
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases
BACKGROUND:Sjögren syndrome is a common, chronic autoimmune disease that typically produces inflammation and poor function of the salivary and lacrimal glands. Other organs can be affected, including the nervous system. Sensory peripheral neuropathy is a common manifestation of the disease. METHODS:Eight-eight patients attending a dry eyes-dry mouth clinic were diagnosed to have primary Sjögren syndrome and underwent a neurological examination. Anti-Ro (or SSA) and anti-La (or SSB) were determined using immunodiffusion as well as Inno-Lia and BioPlex ANA screen. Serum vitamin B(12) levels were determined using an enzyme-linked microtiter plate assay. RESULTS:Twenty-seven (31%) of the 88 patients had peripheral neuropathy as defined by loss of light touch, proprioception, or vibratory sensation. Anti-Ro and anti-La were found by immunodiffusion in 12 patients, and 8 of these 12 had neuropathy (χ(2) = 8.46, P = 0.0036, odds ratio = 6.0 compared to those without precipitating anti-Ro and anti-La). Of the 27 patients with only anti-Ro by immunodiffusion, 13 (48.1%) had neuropathy (χ(2) = 5.587, P = 0.018, compared to those without anti-Ro). There was no relationship of the other, more sensitive measures of anti-Ro and anti-La to neuropathy. In addition, we found no association of serum vitamin B(12) levels to neuropathy among these patients with Sjögren syndrome. CONCLUSIONS:Sensory peripheral neuropathy is common among patients with Sjögren syndrome and is associated with the presence of anti-Ro and anti-La when determined by immunodiffusion.
Neuromyotonia as an unusual neurological complication of primary Sjögren's syndrome: case report and literature review.
Primary Sjögren's syndrome (PSS) is a systemic autoimmune disorder characterized by chronic inflammation of exocrine glands such as the lachrymal and salivary glands, leading to xerophthalmia and xerostomia. Neurological manifestations are sometimes found in patients with PSS. A variety of neurological complications has been reported in patients with PSS, and both the central nervous system (CNS) and peripheral nervous system (PNS) can be involved in PSS. Several forms of neuropathy, including polyneuropathy, cranial neuropathy, and multiple mononeuropathy, are often seen in PSS patients. Herein, we report for the first time typical neuromyotonia (NMT) symptoms appearing in a patient with PSS. Neuromyotonia is a rare disorder caused by the hyperexcitability of peripheral nerves, causing spontaneous and continuous muscle contraction. We provide an overview of the literature relating to neurological involvement in PSS, and the etiology of acquired NMT. We also discuss the existence of contactin-associated protein-like 2 (Caspr2) antibodies in NMT patients.
Diagnosis and treatment of primary Sjögren syndrome-associated peripheral neuropathy: a six-case series.
Yamashita Hiroyuki,Eri Toshiki,Ueda Yo,Ozaki Takashi,Takahashi Hiroyuki,Tsuno Takahiro,Takahashi Yuko,Kano Toshikazu,Mimori Akio
OBJECTIVES:The clinical and therapeutic aspects of primary Sjögren syndrome (PSS) in patients with peripheral neuropathy were analyzed and the specifics of individual case studies are discussed. METHODS:We retrospectively studied six patients (four women, two men; mean age 64.5 years) presenting with PSS with peripheral neurological involvement over a five-year period (2008-2012). All patients had neurological examinations, including nerve conduction studies, somatosensory evoked potentials, and sural nerve biopsies. Treatment regimens included corticosteroids, intravenous gammaglobulin, or immunosuppressive treatment. RESULTS:Peripheral neuropathy was observed in six (7.9 %) of 76 patients with SS as the underlying disease; three were cases of multiple mononeuropathy, two cases had sensory ataxic neuropathy, one of which was autonomic neuropathy, and one case was diagnosed as painful sensory neuropathy without sensory ataxia. Four of the six patients were diagnosed with SS after the onset of neurological symptoms. Individual peripheral neuropathies had distinct neurological, electrophysiological, and pathological characteristics. The effect of steroids and intravenous gammaglobulin differed depending on the case. CONCLUSIONS:In PSS patients, a precise diagnosis is important, because the therapeutic strategy and response varies depending on the type of neuropathy. In clinical practice, it is important to consider a diagnosis of SS when patients present with peripheral neuropathy.
Peripheral neuropathies in Sjögren's syndrome: a critical update on clinical features and pathogenetic mechanisms.
Pavlakis P P,Alexopoulos H,Kosmidis M L,Mamali I,Moutsopoulos H M,Tzioufas A G,Dalakas M C
Journal of autoimmunity
Sjögren's syndrome is a systemic autoimmune disease that, apart from exocrine glands, may affect every organ or system. Involvement of different sections of the peripheral nervous system results in a wide spectrum of neuropathic manifestations. Based on distinct clinical, electrophysiological and histological criteria, the types of neuropathies seen in Sjögren's syndrome include: a) pure sensory which presents with distal symmetric sensory loss due to axonal degeneration of sensory fibers; sensory ataxia due to loss of proprioceptive large fibers (ganglionopathy); or with painful dysethesias (small fiber sensory neuropathy) due to degeneration of cutaneous axons. The latter appears to be the most common neuropathy in Sjögren's syndrome and requires skin biopsy for diagnosis to document loss or reduction of nerve fiber density; b) sensorimotor polyneuropathy affecting sensory and motor axons, often associated with severe systemic or pro-lymhomatous manifestations, such as palpable purpura and cryoglobulinemia, and c) rare types that include autoimmune demyelinating neuropathy, mononeuropathy, mononeuropathy multiplex and autonomic neuropathy. In this review, the frequency, prevalence and diagnostic criteria for each neuropathy subset are discussed and possible pathogenetic mechanisms are outlined.
Cerebrospinal Fluid Findings in Neurological Diseases Associated with Sjögren's Syndrome.
Pars Kaweh,Pul Refik,Schwenkenbecher Philipp,Sühs Kurt-Wolfram,Wurster Ulrich,Witte Torsten,Bronzlik Paul,Stangel Martin,Skripuletz Thomas
BACKGROUND:Sjögren's syndrome is a chronic autoimmune-mediated disease that can cause a variety of neurological manifestations. METHODS:This study investigated characteristics of clinical and cerebrospinal fluid (CSF) features in patients with neurological diseases associated with Sjögren's syndrome. Eighty-two patients were examined separately according to the presence of Sjögren's syndrome alone or in combination with other autoimmune diseases. RESULTS:In the 47 patients with primary Sjögren's syndrome, peripheral neuropathy (57%) was found most frequently, followed by the involvement of the central nervous system (CNS; 17%), cranial neuropathy (15%), and myalgia (11%). These patients did not display consistent signs of inflammation in the CSF. Slight pleocytosis of 8-107 cells/µL was found in patients with peripheral neuropathy (9%), cranial neuropathy (20%), and CNS involvement (25%). Oligoclonal bands indicating intrathecal IgG synthesis occurred in 26% of patients with peripheral neuropathy, 20% of patients with cranial neuropathy, and 25% of patients with CNS involvement. CONCLUSIONS:In patients with Sjögren's syndrome and neurological manifestations, inflammatory CSF changes were rarely found and did not show a characteristic pattern irrespective of peripheral or central genesis of neurological deficits. Analysis of the CSF presents therefore an important diagnostic procedure to exclude other autoimmune and infectious diseases.
Peripheral and central nervous system involvement in a patient with primary Sjögren's syndrome: a case report.
Ging Kathi,Mono Marie-Luise,Sturzenegger Mathias,Zbinden Martin,Adler Sabine,Genitsch Vera,Wagner Franca
Journal of medical case reports
BACKGROUND:Primary Sjögren's syndrome is the second most common rheumatological disorder after rheumatoid arthritis. It typically presents as xerophthalmia and xerostomia in postmenopausal women. Involvement of the central nervous system has been recognized, although its pathogenesis and characteristics are poorly understood. Central nervous system complications are a diagnostic challenge and emphasize the need for systematic screening of patients with new peripheral and central neurological symptoms. CASE REPORT:We report a case of a 58-year-old Swiss woman presenting with rapidly progressive sensorimotor distal polyneuropathy together with new-onset generalized seizures. Initial magnetic resonance imaging (MRI) of the brain performed after the first seizure showed multiple, bihemispheric, confluent white matter hyperintensities with contrast enhancement. Follow-up imaging 3 days after the initial magnetic resonance imaging demonstrated a fulminant disease progression associated with the serious clinical deterioration of the patient. In light of the results of a minor salivary gland biopsy, autoantibody testing, nerve conduction studies, and cranial magnetic resonance imaging, primary Sjögren's syndrome with cryoglobulinemia type II was diagnosed. Response to plasmapheresis and subsequent administration of cyclophosphamide was favorable. CONCLUSION:Even though exocrinopathy is the hallmark of Sjögren's syndrome, systemic symptoms are observed in one-third of patients. There is an urgent need to better characterize the mechanisms underlying different disease phenotypes and to perform randomized controlled trials in order to provide tailored and evidence-based treatment for primary Sjögren's syndrome.
Acute motor and sensory axonal neuropathy associated with Sjögren's syndrome.
Ethemoglu Ozlem,Kocatürk Özcan,Zeynep Emine
Sjögren's syndrome (SS) is an autoimmune disease with mononuclear cell infiltration and destruction of the lacrimal gland and salivary glands, which cause dryness of the eyes and mouth. The most common neurological condition seen in SS is peripheral neuropathy. Initial manifestation of SS as an acute fulminant peripheral neuropathy is extremely rare. We report a 42-year-old patient presenting with acute motor sensory-axonal neuropathy in the presence of SS. She showed partial response to intravenous immunoglobulin but favourable clinical improvement was seen after initiation of corticosteroid treatment.
Classification and characterisation of peripheral neuropathies in 102 patients with primary Sjögren's syndrome.
Brito-Zerón Pilar,Akasbi Miriam,Bosch Xavier,Bové Albert,Pérez-De-Lis Marta,Diaz-Lagares Candido,Retamozo Soledad,Gandía Myriam,Pérez-Alvarez Roberto,Soto-Cárdenas Maria-Jose,Sisó Antoni,Valls-Solé Josep,Graus Francesc,Ramos-Casals Manuel
Clinical and experimental rheumatology
OBJECTIVES:This paper aims to analyse the etiology, characterisation and outcomes of the different types of peripheral neuropathy in patients with primary Sjögren's syndrome (SS) and their association with clinical and immunological disease expression. METHODS:A total of 563 consecutive patients diagnosed with primary SS were evaluated. We retrospectively assessed the results of nerve conduction studies carried out in patients with suspected peripheral nervous system involvement. Peripheral neuropathies were classified into mononeuropathy, mononeuropathy multiplex, polyneuropathy and neuronopathy according to the patterns evidenced by electrodiagnostic studies. RESULTS:Nerve conduction studies were carried out in 158/563 (28%) SS patients. The results were normal in 49 and abnormal in 109 patients, in whom peripheral neuropathy was diagnosed in 102. After excluding patients with neuropathy associated with other diseases and patients with entrapment mononeuropathies, 55/563 (10%) patients were classified as having SS-related peripheral neuropathy, including axonal sensorimotor polyneuropathy (n=24), pure sensory neuronopathy (n=15), mononeuropathy multiplex (n=15) and demyelinating polyradiculoneuropathy (n=1). In spite of therapy, clinical progression measured by the MOHS scale was observed in 12% of patients with axonal polyneuropathy, 13% of those with mononeuropathy multiplex and 47% of those with neuronopathy. Survival was significantly reduced in patients with peripheral neuropathy (especially in those with mononeuropathy multiplex and axonal polyneuropathy) in comparison with the control group (log rank =0.001). CONCLUSIONS:We found a prevalence of SS-related peripheral neuropathy of 10%. Classification of neuropathy according to the clinical presentation and electrodiagnostic tests may be useful in determining the functional outcome, therapeutic response and survival.
[Sjogren's syndrome-associated neuropathy].
Koike Haruki,Sobue Gen
Brain and nerve = Shinkei kenkyu no shinpo
Sjogren's syndrome is a systemic autoimmune disease characterized by xerophthalmia and xerostomia; it is associated with widespread systemic visceral involvement. A wide variety of neurological complications are characteristic features of Sjogren's syndrome, of which peripheral neuropathy is a major neurological manifestation. Based on the predominant neuropathic symptoms, patients can be considered to have several forms of neuropathies, including sensory ataxic neuropathy, painful sensory neuropathy without sensory ataxia, multiple mononeuropathy, multiple cranial neuropathy, trigeminal neuropathy, autonomic neuropathy, and radiculoneuropathy. Acute or subacute onset is observed more frequently in multiple mononeuropathy and multiple cranial neuropathies, whereas disease progression is usually chronic in other forms of neuropathies. Sensory symptoms without substantial motor involvement are observed predominantly in sensory ataxic, painful sensory, trigeminal, and autonomic neuropathies. In contrast, motor impairment is apparent in multiple mononeuropathy, multiple cranial neuropathy, and radiculoneuropathy. Autonomic symptoms such as abnormal pupils and orthostatic hypotension are particularly noted in patients with sensory ataxic, painful, trigeminal, and autonomic neuropathies. Sural nerve biopsy specimens reveal predominantly large fiber loss in sensory ataxic neuropathy and predominantly small fiber loss in painful sensory neuropathy. Vasculitis is observed most frequently in multiple mononeuropathy. The autopsy findings of patients with sensory ataxic and painful neuropathies demonstrate neuronal loss in the dorsal root ganglia and sympathetic ganglia with CD8-positive cytotoxic T lymphocytes. Differential therapeutic responses to corticosteroids and intravenous immunoglobulin can be seen among the various neuropathic forms. In conclusion, the clinicopathological features of neuropathies associated with Sjogren's syndrome are highly variable. The neuropathy classification is important from a therapeutic point of view.
Neuro-Sjögren: Peripheral Neuropathy With Limb Weakness in Sjögren's Syndrome.
Seeliger Tabea,Prenzler Nils K,Gingele Stefan,Seeliger Benjamin,Körner Sonja,Thiele Thea,Bönig Lena,Sühs Kurt-Wolfram,Witte Torsten,Stangel Martin,Skripuletz Thomas
Frontiers in immunology
Sjögren's syndrome is a heterogeneous inflammatory disorder frequently involving peripheral nerves with a wide spectrum of sensory modalities and distribution patterns. The objective of this cross-sectional study was to determine characteristics of Sjögren's syndrome as a cause for severe neuropathy with limb weakness. One hundred and eighty four patients with polyneuropathy associated with limb weakness underwent routine diagnostics including investigations for Sjögren's syndrome. Forty-four patients with Sjögren's syndrome (ACR-EULAR classification criteria) and severe neuropathy were identified. Sjögren's syndrome was found at a median age of 63 years and the gender distribution showed a balanced female-male ratio of 1:1. Anti-SSA(Ro) antibodies were detected in 48% while seronegative patients were diagnosed with Sjögren's syndrome based on sialadenitis on minor salivary gland biopsy with a focus score ≥1. The majority of patients (93%) were diagnosed with Sjögren's syndrome after neurological symptoms appeared. Limbs were symmetrically involved in 84% of patients (57% tetraparesis, 27% paraparesis). Sensory function was not affected in 11% of patients indicating that Sjögren's syndrome associated neuropathy can present as a pure motor syndrome. Electrophysiological measurements did not reveal pathognomonic findings (23% demyelinating pattern, 36% axonal pattern, 41% both demyelinating and axonal damage signs). More than half of our patients fulfilled the European Federation of Neurological Societies (EFNS) diagnostic criteria for CIDP indicating that distinction between Neuro-Sjögren and other causes of neuropathy such as CIDP is challenging. Our findings show that severe neuropathy with limb weakness is often associated with Sjögren's syndrome. This is of great importance in identifying and understanding the causes of immune mediated polyneuropathy.
The association between serological biomarkers and primary Sjogren's syndrome associated with peripheral polyneuropathy.
Hsu Che-Wei,Su Yu-Jih,Chang Wen-Neng,Tsai Nai-Wen,Chiu Wen-Chan,Cheng Ben-Chung,Su Chih-Min,Huang Chi-Ren,Chang Ya-Ting,Lu Cheng-Hsien
BioMed research international
BACKGROUND AND AIM:The sensitivity and specificity of biomarkers used for predicting peripheral neuropathy of Sjogren's syndrome (SJS) patients remain unsatisfactory. This study aimed to determine the prognostic value of circulating autoantibodies levels in SJS patients with peripheral neuropathy. METHODS:Two hundred and fifty serological positive (either anti-Ro or anti-La positive) SJS patients' data were collected retrospectively. The titers of autoantibodies, electrophysiology reports, and clinical manifestation were reviewed. RESULTS:The prevalence rate of peripheral neuropathy is 7.2% in our study. Regarding classification of peripheral neuropathy, 12 had mixed sensorimotor polyneuropathy, six had cranial neuropathy. After stepwise logistic regression analysis, anti- β 2 glycoprotein I (a β 2GP I) and perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) were significantly associated with peripheral neuropathy in serology positive SJS (P = 0.01, P = 0.046, resp.). CONCLUSION:The occurrence of peripheral neuropathy among SJS patients is not frequent and easily overlooked. Our study demonstrated that a β 2GP I and p-ANCA levels may imply the danger of the occurrence of neuropathy in SJS patients, and they can be considered a biomarker that should be added to the panel of conventional autoantibody in SJS patients.