Intracranial hypertension as the first manifestation of primary Sjögren’s syndrome

Introduction

Idiopathic intracranial hypertension is a clinical syndrome characterized by raised intracranial pressure without any identifiable pathology in the brain and with normal cerebrospinal fluid (CSF) composition. Headaches are the most common symptom and papilledema is the cardinal sign (1).

Central nervous system (CNS) manifestations are uncommon in patients with primary Sjögren’s syndrome (pSS), although peripheral nervous system (PNS) involvement is well known. Nervous system involvement includes symptomatic brain lesions, meningitis, myelopathy, and cranial neuronopathy (2).

Here, a patient with pSS that initially presented with intracranial hypertension is reported.

Case

A 19-year-old man complained of binocular horizontal diplopia and headaches for 20 days prior to presentation. He reported having been well before the onset of symptoms including blurred vision and diplopia. His previous medical history was unremarkable and there was no history of exposure to drugs.

Physical examination revealed a well-appearing non-obese male (body mass index [BMI]: 22.7). The findings on the neurological examination were normal except for bilateral abducens nerve palsy. The intraocular pressure was normal in both eyes and the fundi showed bilateral hyperemic disk swelling with normal retinal vessels (Figure 1). The lumbar puncture had an opening pressure of 35 cmH₂O, with a leukocyte count of 1/mm³, a protein level of 44.2 mg/dl and a glucose level of 55 mg/dl. The brain MRI, MR angiography and venography were normal. Laboratory studies, including a complete blood count, blood chemistry, thyroid function testing, venereal disease research laboratory testing, coagulation battery, HIV antibodies and vitamin A level, were all normal. The ANA screen was positive with a titer of 1 : 400 with speckled and nucleolar patterns. The IgM rheumatoid factor was positive at 172 U/ml and SS-A native (60 kDa) and SS-B were present and graded 3+. Further autoimmune testing included anticardiolipin antibodies, lupus anticoagulant antibodies, anti-Scl antibodies anti-ss-DNA IgG, antineutrophil cytoplasmic antibodies, RNP/Sm, Sm, Pm-Scl, Jo-1, centromere B, PCNA, nucleosomes, histones, ribosomal-P protein and AMA-M2 antibodies. The results of these tests were all normal. A subsequent salivary gland scan revealed mildly impaired uptake of the parotid and submandibular glands, bilaterally. Ocular dryness was confirmed by the Schirmer test (<5 mm in 5 minutes). A biopsy specimen was obtained from accessory salivary glands and revealed a diffuse infiltrate of lymphoplasma cells, indicative of lymphocytic sialadenitis. OPEN IN VIEWER

Based on these findings, the patient was diagnosed with pSS. Treatment with acetazolamide 1.5 g daily and prednisone 60 mg daily was started. During the following two weeks the diplopia and headache resolved. The acetazolamide and prednisone were tapered over six months and the papilledema gradually resolved after treatment. Since then, the patient was treated with 5 mg pilocarpine for sicca syndrome and was well without relapse of CNS symptoms during the following 12 months. The follow-up titers of autoimmune antibodies were also restored to normal ranges.

Discussion

Intracranial hypertension syndrome is characterized by increased intracranial pressure and papilledema not associated with focal neurological signs. There are many conditions associated with the intracranial hypertension syndrome, though most cases are diagnosed as idiopathic (1). Intracranial hypertension syndrome is included among the extremely rare neurological manifestations of rheumatological diseases. Although various mechanisms have been proposed (e.g. venous thrombosis, medication side effects and immunological or inflammatory disease), none have been proven to be causal (3–6).

CNS involvement is rarely associated with pSS, and therefore, is easily overlooked. However, a recent report suggested that CNS involvement with pSS is more frequent and is variable in its presentation (7). In addition, CNS symptoms can be the initial manifestation of pSS when mild complaints of sicca symptoms are overlooked (7). As in this case, the presence of bilateral papilledema without any identifiable pathology in the brain, and with compatible laboratory and pathology findings consistent with pSS, the diagnosis of Sjögren’s syndrome was suggested. Given that the symptoms resolved after steroid treatment, the intracranial hypertension may have been associated with the abnormal activity of pSS. However, the improvement of symptoms cannot be explained solely by disease activity; this is because the patient was concurrently treated with 1.5 g of acetazolamide, and had undergone a lumbar puncture with presumably a much lower closing CSF pressure.

There are no prior case reports of intracranial hypertension syndrome as the presenting symptom of Sjögren’s syndrome. One case report presents a patient with Sjögren’s syndrome who developed intracranial hypertension with other systemic manifestations of pSS (8). Another case of a patient with Sjögren’ syndrome reported symptoms of the intracranial hypertension syndrome that developed and led to a secondary diagnosis of systemic lupus erythematosus (9). The pathophysiological mechanism of intracranial hypertension in pSS remains unknown. In several cases associated rheumatological diseases, intracranial hypertension has been attributed to cerebral venous thrombosis (3,4). The patients in these cases had lupus anticoagulant or anticardiolipin antibodies that were assumed to induce a hypercoagulable state (3,9). Another possible mechanism might be associated with vasculitis, immune complex precipitation or even direct antibody injury which may result in a similar dysfunction (10). In this patient, the testing for serum anticardiolipin antibody and lupus anticoagulant were negative and there was no evidence of venous sinus thrombosis on the MRI scans. The laboratory and radiological findings along with the clinical history in this patient favored the latter hypothesis as a causative condition.

In conclusion, a rare case of primary Sjögren’s syndrome complicated by intracranial hypertension syndrome is reported. This case illustrates that Sjögren’s syndrome should be considered in the differential diagnosis of intracranial hypertension syndrome.