Role of anti-calcium channel and anti-receptor autoantibodies in autonomic dysfunction in Sjögren's syndrome

Auto-antibodies cross-reacting with L-type voltage-gated calcium channels (VGCCs) have been described in primary Sj?gren's syndrome (pSS), and may mediate the cardiac defects in neonates born to mothers with pSS. L-type VGCCs are also present in autonomically innervated tissues. Therefore, the aim of this project was to investigate a role for anti-VGCC antibodies and antibodies to alpha(1)-adrenoceptors or P(2X)-purinoceptors in the autonomic dysfunction that occurs in pSS. Contraction of the sympathetically innervated vas deferens in response to stimulation of the muscle by an alpha(1)-adrenoceptor agonist (phenylephrine) or a P(2X)-purinoceptor agonist (alpha,beta-methylene ATP) was measured in the absence and presence of 2% serum. Contractions produced by phenylephrine and by alpha,beta-methylene ATP were abolished by nicardipine, demonstrating that they are coupled to calcium influx through L-type VGCCs. Serum from patients with pSS or from healthy controls did not significantly alter the L-type channel-dependent responses of smooth muscle to agonist stimulation. We therefore conclude that pSS serum does not contain autoantibodies that functionally inhibit L-type VGCCs, alpha(1)-adrenoceptors or P(2X)-purinoceptors in smooth muscle and that such autoantibodies cannot explain the autonomic dysfunction in pSS.     

Plasmapheresis in the treatment of ataxic sensory neuropathy associated with Sjögren's syndrome

Sj?gren's syndrome (SS) is an important but poorly recognized cause of peripheral neuropathy. Several forms of peripheral nerve dysfunction occur, including trigeminal sensory neuropathy, mononeuropathy multiplex, distal sensorimotor polyneuropathy and pure sensory neuronopathy. The pathological findings vary and the definite treatment is not known. Here we present 4 cases of acute ataxic sensory polyneuropathy with SS, and the experience of treatment with plasmapheresis (PP). The 4 patients were all females; ages ranged from 30 to 58 years. All had prominent loss of kinesthetic and proprioceptive sensation. The course ranged from acute to subacute onset. Patients were treated with 5-9 sessions of PP. Two patients with initiation of treatment within 2 weeks of onset showed dramatic and sustained responses after PP, while the other 2 had no detectable effects. Our experience showed that PP should be considered in patients who present with sensory neuropathy associated with SS, and the treatment should be given as early as possible.     

Myelopathy in primary Sjögren's syndrome: diagnostic and therapeutic aspects

We report a patient with a myelopathy in primary Sjögren's syndrome, proven by salviary gland biopsy and specific antibodies. Under steroid medication, the patient had a remitting and relapsing clinical course. The severity of clinical symptoms correlated with a transient contrast uptake in spinal magnetic resonance imaging. Under a treatment with azathioprine and prednisone the patient has suffered no relapse within the last 20 months. Although this is only a case report, the combination of azathioprine and prednisone may be a valuable medication in chronic cases of Sjögren's syndrome with neurologic symptoms.     

Neuropsychological, neuroimage and psychiatric aspects of primary Sjögren's syndrome

We report a case of a 49-year-old woman diagnosed with primary Sj?grens Syndrome (pSS) who was submitted to extensive neuropsychobiological assessment. Examination revealed a Wechsler Adult Intelligence Scale-Revised (WAIS-R) Full Scale IQ of 97 with no Verbal/Performance IQ discrepancy and performance below estimated premorbid levels on arithmetic skills, visual tracking, naming and delayed paired associate learning/memory. CT scans of the brain were normal. However, there were subcortical hyperintensities on MRI and left parieto-temporal hypoperfusion on SPECT. Neuropsychological impairment is consistent with the pattern of neuroimage findings. We hypothesize that the pathophysiological mechanisms of pSS involve direct immune attack on neurons in addition to indirect effects through small-vessel angiopathy and thereby induce natural fracture lines in behavior according to location in the central nervous system.     

Central nervous system Sjögren's syndrome in a child: case report and review of the literature

We describe a case of pediatric Sj?gren's syndrome with progressive neurologic involvement. At age 4 years, she had been diagnosed with Melkersson-Rosenthal syndrome. After being stable with facial diplegia and swelling for 5 years, she acutely presented with diplopia, vertigo, and ataxia. Cranial magnetic resonance imaging (MRI) showed a left dorsal midbrain lesion. Serologic and histopathologic findings confirmed primary Sj?gren's syndrome. She responded well to intravenous methylprednisolone, with subsequent clinical improvement and MRI resolution. This report reviews the pediatric literature and underscores the importance of considering Sj?gren's syndrome in a child with unexplained facial weakness and in the differential diagnosis of pediatric stroke.     

Peripheral neuropathy in an outpatient cohort of patients with Sjögren's syndrome

Peripheral neuropathy is common in patients with Sj?gren's syndrome (SS), but its precise prevalence is unknown. Most prior studies were conducted at neurology or rheumatology specialty clinics and likely selected for a more severely affected population. We evaluated 22 SS patients and 10 controls for evidence of neuropathy in an outpatient setting at a regional meeting of the Sj?gren's Syndrome Foundation. We performed neurological examinations and nerve conduction studies (NCSs) and measured serum antinuclear antibody (ANA) and SS-A and SS-B antibody levels. Participants filled out a questionnaire pertaining to symptoms, diagnosis, and treatment. We found that signs and symptoms related to small axons were more common in patients with SS than in controls. Complaints of painful distal paresthesias in the feet were noted in 59% of patients but in only 10% of controls, and of abnormal sweating in 41% and 0%, respectively. Examination revealed decreased pinprick sensation in 64% of patients with SS, but in only 30% of controls. Overall, 45% of the patients but none of the controls were thought to have an isolated small-fiber neuropathy. Large-fiber dysfunction (as measured by testing vibration, deep tendon reflexes, and NCSs) was similar between the two groups. We conclude that small-fiber neuropathy is common in patients with SS.     

Platelet serotonin in primary Sjögren's syndrome: Level and relation with disease activity

Primary Sj?gren's syndrome (pSS) is chronic autoimmune disorder of unknown ethiopathogenesis. In line with the concept of neuroimmunohormonal dysregulation in inflammatory rheumatic diseases, the aim of this study was to investigate platelet serotonin level (PSL) in patients with pSS and its relation with the activity and duration of the disease. Significantly lower PSL in pSS patients (N=61) was shown as compared to healthy controls (N=103). No correlation was found between PSL and the actual disease activity assessed by the recently developed EULAR Sj?gren's Syndrome Disease Activity Index (ESSDAI). Results suggest involvement of the serotonin system in the pathogenesis of pSS.     

Defective metabolism of leukotriene B4 in the Sjögren-Larsson syndrome

The Sj?gren-Larsson Syndrome (SLS) is a neurocutaneous disorder, caused by deficient activity of the microsomal enzyme fatty aldehyde dehydrogenase (FALDH). FALDH catalyzes the oxidation of medium- and long-chain fatty aldehydes to their corresponding carboxylic acids. SLS is diagnosed by demonstrating the enzyme deficiency or by mutation analysis of the FALDH gene, while laboratory investigations of plasma, urine, and cerebrospinal fluid do not reveal any diagnostic abnormality. Leukotriene (LT) B4 is a pro-inflammatory mediator synthesized from arachidonic acid. LTB4 is inactivated by microsomal omega-oxidation, successively yielding 20-OH-LTB4, 20-CHO-LTB4 and 20-COOH-LTB4. Since FALDH is involved in LTB4 degradation, we have analyzed LTB4 and its metabolites in urine and cerebrospinal fluid as well as the degradation capacity for LTB4 in fresh polymorphonuclear leukocytes (PMN) of SLS patients. The urinary concentrations of LTB4, 20-OH-LTB4 and 20-COOH-LTB4 are below the detection limit in healthy controls. The urine of all SLS patients (n=13) exhibited highly elevated concentrations of LTB4 and 20-OH-LTB4, while 20-COOH-LTB4 was absent. Cerebrospinal fluid levels of LTB4, 20-OH-LTB4 and 20-COOH-LTB4 were found to be normal (n=7). PMN isolated from four patients were shown to be unable to convert 20-OH-LTB4 to 20-COOH-LTB4. Our findings provide unambiguous evidence for defective LTB4 degradation in SLS patients, and offer new and non-invasive diagnostic tools. Moreover, they open new pathophysiological considerations, with the prospect of rational treatment strategies.     

Sensory neuropathy of the trigeminal, glossopharyngeal, and vagal nerves in Sj?gren's syndrome.

Isolated cranial nerve involvement in primary Sj?gren's syndrome (primary SS) has rarely been described. We report the case of a patient with sensory neuropathy of the trigeminal and also the glossopharyngeal and vagal nerves, which has not been identified previously. The electrophysiological findings in our patient with primary SS confirmed trigeminal sensory neuropathy with abnormal blink reflexes and abnormal cutaneous masseter inhibitory reflexes.     

High frequency of primary Sjögren's syndrome in Taiwanese patients presenting as relapsing-remitting multiple sclerosis

Primary Sj?gren's syndrome (PSS) with central nervous system involvement may mimic the manifestations of multiple sclerosis (MS). The prevalence of PSS in MS patients varies in the published literature (0-16.6%), but has not yet been investigated in Asia, having a much lower MS prevalence than Western countries. Twelve consecutive patients presenting with a relapsing-remitting MS-like syndrome were recruited to assess the presence of PSS according to the American-European consensus group criteria. Six patients (50%) fulfilled the diagnostic criteria of PSS. The preliminary result suggests that PSS is an important differential diagnosis in patients with MS-like syndrome in Taiwan. The prevalence of 'pure MS' in Taiwan might be even lower than expected. A further large-scale study is warranted to confirm this finding in Taiwan as well as other Asian countries.     

Treatment of myelopathy in Sjögren syndrome with a combination of prednisone and cyclophosphamide

BACKGROUND: Peripheral neuropathy is a common complication of primary Sj?gren syndrome, but central nervous system involvement also occurs and may be the only extraglandular manifestation. Sicca symptoms may also be minimal. Combinations of lesions along with relapses and remissions can suggest multiple sclerosis in the proper clinical setting, making the correct diagnosis elusive. OBJECTIVES: To report a case of progressive transverse myelopathy with previous optic neuropathy in primary central nervous system Sj?gren syndrome (CNS-SS), and to review 17 previously reported cases and the patient's responses to various therapies. DESIGN: Case report and literature review. SETTING: University hospital. PATIENT: A 63-year-old Hispanic woman with a 10-month history of progressive spastic paraparesis associated with optic neuropathy and a T10 sensory level. Magnetic resonance imaging demonstrated multifocal, contrast-enhancing lesions in the spinal cord. The patient was diagnosed as having CNS-SS because of the presence of sicca symptoms, abnormal serological test results, and salivary gland biopsy results, which fulfilled San Diego criteria for "definite" Sj?gren syndrome. She responded to treatment with a combination of prednisone and cyclophosphamide. CONCLUSIONS: Diagnosis of primary CNS-SS requires a high index of suspicion and specialized clinical testing. Treatment with pulse doses of corticosteroids alone may be suboptimal, but results of treatment with a combination of corticosteroids and either cyclophosphamide or chlorambucil have been encouraging.     

Long time interval between multiple sclerosis onset and occurrence of primary Sjögren's syndrome in a woman treated with interferon-beta

Primary Sjögren's syndrome (SS) with central nervous system involvement can clinically mimic multiple sclerosis (MS). However, SS and MS may coexist. We report here a case of a 48‐year‐old woman affected by relapsing–remitting MS, good responder to interferon (IFN)‐beta 1a, developing sicca complex after 29 years from MS onset. At the age of 48, after 5 years successful treatment with i.m. IFN‐beta 1a, xerophtalmia and xerostomia with dysphagia occurred. Autoantibody screening for connective tissue diseases, including anti‐ENA, was negative. Schirmer's test showed reduced lacrimal gland function and a minor salivary gland biopsy showed chronic inflammatory infiltration with fibrosis, acinar atrophy and ductal ectasia. According to clinical and pathological findings a diagnosis of SS was made. Other cases of connective tissue diseases after IFN‐beta treatment have been described. However, this is, to our knowledge, the first report on the development of primary SS after long time interval from MS onset in a woman treated with IFN‐beta. Although there are no evidences about a possible role of IFN‐beta in triggering SS yet, a screening for clinical and laboratory signs of SS should be assessed in MS patients during IFN‐beta treatment.