Severe Peripheral Neuropathy in a Young Female with Primary Sjogren’s Syndrome

Original Article

Austin J Clin Neurol 2020; 7(1): 1138.

Severe Peripheral Neuropathy in a Young Female with Primary Sjogren’s Syndrome

Mirica R¹* and Soare I²

¹Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Romania

²Faculty of Medicine, Titu Maiorescu University, Romania

*Corresponding author: Roxana Mirica, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 60, Grigore Alexandrescu Street, District 1, zip code 010626, Bucharest, Romania

Received: April 29, 2020; Accepted: May 19, 2020; Published: May 26, 2020


Neurological disorders represent one of the most common extraglandular manifestations may be found in patients with Sjogren’s syndrome. In this paper we will present the case of a 43-year-old patient with symptomatic onset characterized by paresthesia with “stocking-glove” distribution, evolving with severe ataxia. Clinical examination revealed disturbances of proprioceptive sensitivity in both thoracic and pelvic limbs. The titer of antinuclear antibodies was 1/320, Anti-Ro (SS-A) antibodies were positive, and the biopsy of minor salivary glands showed histopathological changes. The patient underwent repeated electromyography examinations that revealed sensory axonal polyneuropathy. SICCA symptoms started several years after the onset of the first neurological manifestations, and the Schirmer’s test was ‘borderline’. Corroboration of clinical and paraclinical data led to the diagnosis of primary Sjogren’s syndrome with sensory axonal polyneuropathy. The administration of Plaquenil (Hidroxychloroquine sulfate), intravenous immunoglobulin, glucocorticoids, plasmapheresis, Mycophenolate mofetil, Belimumab and Rituximab did not improve neurological complaints, the peripheral neuropathy being refractory to treatment.

Keywords: Primary sjogren’s syndrome; Sensory axonal polyneuropathy; Severe ataxia


Sjogren’s syndrome is an autoimmune disorder affecting the exocrine glands [1], associated with peripheral nervous system manifestations, with sensory neuropathy as one of the most common neurological forms [2].

Sjögren’s syndrome, in both primary and secondary forms, is defined as a chronic [3], multisystemic disease of unspecified etiology, and is more common in middle-aged women (aged 40-50) [1]. The primary type is characterized by the involvement of exocrine glands with or without systemic complications, and the secondary form is associated with other autoimmune diseases [1]. Peripheral nervous system involvement is the consequence of neuronal damage by immunological mechanism [2], such as apoptosis, antibody expression, B and T cell changes, and cytokine levels [4,5]. We present a clinical case of primary Sjogren’s syndrome with severe sensory axonal polyneuropathy.

Methods and Materials

43-year-old M.I. patient with significant family history (motherrheumatoid arthritis and mixed connective tissue disease, auntrheumatoid arthritis), with dyslipidemia, tenosynovitis in both radiocarpal joints operated in 2005 and 2006, is admitted to a clinical hospital in Bucharest for symptoms started in December 2010, consisting of paresthesia with distal onset, predominantly in the left hemibody, both in the thoracic limbs, “glove”-like (with progression up to 2/3 left arm and right elbow), and in the pelvic limbs, “stocking”- like (with progressive evolution up to the knee), as well as on the face. In 2011, the patient complains of the occurrence of related symptoms such as unsteady gait, intense vertigo accompanied by nausea without vomiting, balance and coordination disorders, dysarthria, decreased concentration, important physical asthenia, right ear tinnitus associated with bilateral hearing loss and visual impairment with ‘blurred vision’ in the right eye. It also associates muscle twitching and atrophies at the level of the pelvic limbs and hypotonia. To investigate these signs and symptoms, several electromyography examinations were performed in April, June and December 2011, and the diagnosis was axonal sensitive polyneuropathy. The patient also states the presence of Raynaud’s phenomenon, urinary urgency and chronic constipation, symptoms with an onset of approx. 2 years.

In 2012, the suspicion of an antiphospholipid syndrome was raised, with positive anti-beta-2 glycoprotein antibodies and neuroborreliosis (based on dark field microscopy), but without increased serum antibody titer, disproved by the cerebrospinal fluid result (cellularity, proteinorrachia, glycorrhachia–within normal limits), for which she received repeated courses of antibiotics that suddenly worsened the symptoms, with significant weight loss, so that the patient was able to move only with the help of another person.

In 2014, the diagnosis of primary Sjogren’s syndrome was established based on the presence of anti-Ro antibodies and antinuclear antibodies and on the performed biopsies (of minor salivary gland and sural nerve and gastrocnemius muscle). The histopathological appearance of the salivary gland fragment examined revealed focal sialadenitis with predominantly B lymphocytes. The biopsy of the left sural nerve showed signs of severe axonal polyneuropathy manifested morphologically by decreased density of myelin fibers, at 1,987 fb/mm2 (N=7,000-11,000 fb/m2), 34% fibers with myelinic ovoids and bullae and 15% fibers with segmental demyelination lesions of the total dissociated myeloid fibers. The microscopy of the left gastrocnemius muscle showed muscle lesions of neurogenic origin with the presence of fibers in necrobiosis.Laboratory tests and investigations for disseminated lupus erythematosus, rheumatoid arthritis, Wegener’s granulomatosis, scleroderma, dermatomyositis, polymyositis did not confirm all these diagnoses. Serum protein electrophoresis, immunogram, thyroid hormones, HBs Ag, anti-HVC antibodies, HIV, anti-neuronal antibodies, anti-MAG antibodies, anti-ganglioside antibodies, anti-cardiolipin antibodies Ig M and Ig G, anti-β2 glycoprotein antibodies Ig G, anti-Sm antibodies, anti-La antibodies, anti-p ANCA antibodies, anti-centromere antibodies, anti-SCL 70 antibodies, ndc DNA, C-reactive protein, rheumatoid factor, serum complement C3, C4 were within normal limits with positive result for ribosomal P protein. At the same time, Schirmer’s test was ‘borderline’ and cryoglobulinemia and lupus cells–absent. The patient also performed visual and auditory evoked potentials that revealed long-latency potentials. Cerebral and cervical-dorsallumbar spine MRI with contrast agent excluded other presumptive diagnoses, such as multiple sclerosis, with no evidence of central nervous system demyelination. In April 2018, the patient is diagnosed with chronic autoimmune thyroiditis-subclinical hypothyroidism, for which Euthyrox treatment is administered, 25 μg/day. During the same period, manifestations of SICCA syndrome-xerostomia and xerophthalmia (approximately 7 years after the onset of the first neurological complaints) occurred.

The objective examination upon re-admission in September 2019 revealed pale skin, livedo reticularis at the distal extremities, underweight, no joint swelling, no rash, pulmonary auscultation without added crackles, cardiac without added murmurs, no orthostatic hypotension phenomena, supple abdomen, mobile with respiration, spontaneous or palpation painlessness, physiological micturition, negative costovertebral angle tenderness test.

Neurological examination highlighted the following aspects: conscious patient, no neck stiffness, ataxic gait with wide base, with unilateral support, unsystematic positive Romberg, left hemifacial hypoesthesia, left>right brachial tetraparesis, right>left crural, severe crural>brachial sensory tetra-ataxia, right>left, overall abolished osteotendinous reflexes, cutaneous plantar reflexes in bilateral flexion, paresthesia with “glove”-like and “stocking”-like numbness left>right, superficial hypoesthesia up to the elbow of the left thoracic limb and right forearm and crural up to the ½ level of left thigh and right knee and deep left>right, mild dysarthria, muscle atrophies in the hands, forearm, chest, continent sphincters. The Electroencephalography (EEG) showed a dominant alpha rhythm in the posterior derivations, blocked at the spontaneous opening of the eyes and at hyperventilation, no electrical paroxysms, no interhemispheric abnormalities. The numerous EMG examinations which our patient undergone led to the diagnosis of sensory axonal polyneuropathy, with no dramatic evolution in the appearances of the pathways throughout this period (Figure 1). The patient did not show psychopathological symptoms of a particular appearance at the psychological examination, without clinically significant cognitive impairment, with a score of 30 points following the MMSE (Mini- Mental State Examination) test and 13 BDI (Beck’s Depression Inventory) points.