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Nine syndrome in a patient with systemic lupus erythematosus

Published:September 22, 2017DOI:https://doi.org/10.1016/j.jcjo.2017.07.018
      Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many different organ systems and present in a variety of ways. The central nervous system (CNS) is frequently affected, resulting in a wide range of manifestations. Patients may present to an ophthalmologist with ocular symptoms before a diagnosis is established; thus, early recognition is important to avoid delays in diagnosis and treatment. We report the first case of a patient with lupus who developed nine syndrome due to pontine ischemic stroke precipitated by CNS vasculitis.

      Case Report

      A 29-year-old male presented to the ophthalmology clinic with a 1-month history of painless gaze-dependent binocular diplopia and oscillopsia, right-sided facial palsy, and left-sided hemiparesis in addition to a 2-year history of remitting and relapsing constitutional and systemic symptoms. He was initially worked up for Sjogren’s syndrome 2 years earlier when he presented with parotid gland inflammation and had positive serum anti-Sjogren's syndrome B antigen (SSB) antibodies. Then, 6 months before presenting to clinic, he developed flu-like symptoms, including cough, fever, chills, and fatigue. A rapid flu test was positive, and he was treated with oseltamivir. Thereafter, his constitutional symptoms remitted and relapsed, and he developed the following symptoms: generalized joint pain; an erythematous malar rash extending to his thorax, arms, and back; alopecia; photosensitivity; and mouth ulcers. He saw several clinicians and received various diagnostic studies. He was found to be anemic and pancytopenic on complete blood count (CBC). Bone marrow biopsy showed no evidence of malignancy; upper gastrointestinal endoscopy showed no bleeding but did reveal findings concerning for Candida esophagitis. A computed tomography scan of the chest revealed axillary and retropectoral lymphadenopathy and pleuritis. A month before presentation, he began noticing blurry vision in the right eye. His symptoms progressed and he developed diplopia, oscillopsia, facial palsy, and hemiparesis.
      On examination, visual acuity was 20/25 OU. Colour vision was normal (14/14 Ishihara plates). Pupils were equal, round, and reactive to light with no relative afferent pupillary defect (RAPD). Visual fields were full to confrontation. Slit-lamp examination revealed interpalpebral punctate epithelial erosions on the right cornea. Findings of fundus examination were normal. Motility examination revealed a small primary position esotropia, right conjugate horizontal gaze palsy, and limited adduction of the right eye suggestive of one-and-a-half syndrome on the right (Fig. 1). Additionally, there was normal convergence with negative doll’s head manoeuvre and a horizontal abducting nystagmus on attempted left gaze. External examination showed right-sided lower motor neuron facial palsy with lagophthalmos (Fig. 1). Neurologic examination revealed left-sided hemiparesis.
      Fig. 1
      Fig. 1Motility examination showing a small primary position esotropia, bilateral right gaze palsy, mild right eye adduction deficit, and normal up gaze and down gaze (A). External examination showing right-sided facial palsy with lagophthalmos (B).
      Magnetic resonance imaging (MRI) of the brain revealed a contrast-enhancing lesion in the dorsal right pons with ventral, rostral, and caudal extension consistent with a pontine ischemic stroke (Fig. 2). Electrocardiogram and echocardiogram showed no evidence of arrhythmia, endocarditis, or thrombus. Metabolic, hematologic, coagulative, and infectious studies were unremarkable. Autoimmune studies were positive for serum antinuclear antibodies, anti-Smith antibodies, and anti–double-stranded DNA antibodies, as well as low complement levels. Serum antiphospholipid antibody assays were negative. A lumbar puncture with cerebrospinal fluid studies revealed pleocytosis and elevated protein consistent with CNS vasculitis. A standard catheter angiogram also showed findings consistent with CNS vasculitis.
      Fig. 2
      Fig. 2Axial (A) and sagittal (B) views of postcontrast magnetic resonance imaging T1 image of the brain showing an enhancing right dorsal pontine lesion with ventral, rostral, and caudal extension.
      A diagnosis of SLE was made. The patient was started on prednisone, hydroxychloroquine, and cyclophosphamide. On follow-up, his hemiparesis had improved, but his ocular and facial symptoms persisted. The lagophthalmos was managed with an external eyelid weight and lubrication, and the patient is being considered for upper eyelid gold weight insertion as well as strabismus surgery.

      Discussion

      SLE can be a diagnostic challenge because of its widely variable clinical presentation.
      • Thong B.
      • Olsen N.J.
      Systemic lupus erythematosus diagnosis and management.
      The American College of Rheumatology (ACR) classification criteria, last updated in 1997, aid in the timely diagnosis of this disease.
      • Hochberg M.C.
      Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.
      The Systemic Lupus International Collaborating Clinics (SLICC) group updated the criteria in 2012 to reflect the latest knowledge of the disease.
      • Petri M.
      • Orbai A.M.
      • Alarcon G.S.
      • et al.
      Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus.
      The SLICC criteria were found to be more sensitive and thus are now more commonly employed.
      • Ines L.
      • Candida S.
      • Galindo M.
      • et al.
      Classification of systemic lupus erythematosus: Systemic Lupus International Collaborating Clinics Versus American College of Rheumatology Criteria. A comparative study of 2,055 patients from a real-life, international systemic lupus erythematosus cohort.
      This patient fulfilled both criteria but, like many other patients, had a delayed diagnosis, highlighting the diagnostic challenge posed by SLE.
      Patients with lupus commonly develop neurologic manifestations. In 1999, the ACR published a nomenclature system with standardized case definitions for 19 distinct neuropsychiatric syndromes of SLE.
      • Liang M.H.
      • Corzillius M.
      • Bae S.C.
      • et al.
      The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes.
      Cerebrovascular disease is categorized as one of the CNS syndromes. Major CNS involvement is rare but has significant implications. A 3-year prospective study of 370 patients with lupus found that only 4.3% had major CNS involvement, but 13% of all hospitalizations were due to CNS disease.
      • Kampylafka E.I.
      • Alexopoulos H.
      • Kosmidis M.L.
      • et al.
      Incidence and prevalence of major central nervous system involvement in systemic lupus erythematosus: a 3-year prospective study of 370 patients.
      Although there was a 1.4% rate of stroke in all lupus patients, strokes comprised 31% of all CNS disease.
      • Kampylafka E.I.
      • Alexopoulos H.
      • Kosmidis M.L.
      • et al.
      Incidence and prevalence of major central nervous system involvement in systemic lupus erythematosus: a 3-year prospective study of 370 patients.
      Another study found a stroke rate of 5.6% and determined that the most commonly associated factors were hypertension, antiphospholipid antibodies, and Libman-Sacks endocarditis.
      • Kitagawa Y.
      • Gotoh F.
      • Koto A.
      • Okayasu H.
      Stroke in systemic lupus erythematosus.
      The etiology of this patient’s stroke was vasculitis, of which there are only a few reported cases associated with SLE.
      • Goel D.
      • Reddy S.R.
      • Sundaram C.
      • Prayaga A.K.
      • Rajasekhar L.
      • Narsimulu G.
      Active necrotizing cerebral vasculitis in systemic lupus erythematosus.
      A review of 3 large autopsy studies of SLE patients with CNS disease found that between 0% and 13% had true vasculitis.
      • van Dam A.P.
      Diagnosis and pathogenesis of CNS lupus.
      This patient’s pontine stroke precipitated by CNS vasculitis is a rare manifestation of SLE.
      The neuro-ophthalmic findings in this case represent nine syndrome, a rare and recently described pontine ischemic syndrome characterized by internuclear ophthalmoplegia with the addition of cranial nerve 6 palsy (one-and-a-half syndrome), facial paralysis (eight-and-a-half syndrome), and contralateral hemiparesis.
      • Mahale R.R.
      • Mehta A.
      • John A.A.
      • Javali M.
      • Abbas M.M.
      • Rangasetty S.
      “Nine” syndrome: a new neuro-ophthalmologic syndrome: report of two cases.
      There are only 5 reported cases of nine syndrome in the literature.
      • Mahale R.R.
      • Mehta A.
      • John A.A.
      • Javali M.
      • Abbas M.M.
      • Rangasetty S.
      “Nine” syndrome: a new neuro-ophthalmologic syndrome: report of two cases.
      • Rosini F.
      • Pretegiani E.
      • Guideri F.
      • Cerase A.
      • Rufa A.
      Eight and a half syndrome with hemiparesis and hemihypesthesia: the nine syndrome?.
      • Lakhiar M.A.
      • Mughal S.A.
      Eight-and-half syndrome: a rare neuro-ophthalmic syndrome “Possible Nine Syndrome.”.
      • Hansen B.A.
      • Athappilly G.
      Man experiences sudden onset binocular diplopia.
      SLE patients have been reported to present with internuclear ophthalmoplegia and one-and-a-half syndrome due to pontine stroke.
      • Galindo M.
      • Pablos J.L.
      • Gómez-Reino J.J.
      Internuclear ophthalmoplegia in systemic lupus erythematosus.
      • Sasannejad P.
      • Olfati N.
      • Soltani S.M.
      • Juibary G.
      The one-and-a-half syndrome as the presenting sign of systemic lupus erythematosus.
      To our knowledge, however, there are no reports of lupus presenting with either eight-and-a-half syndrome or nine syndrome.
      In conclusion, this is the first reported case of a patient with lupus presenting with nine syndrome due to CNS vasculitis. Although involvement of the CNS in lupus is rare, especially in the case of vasculitis-precipitated stroke, it can lead to devastating results and should be diagnosed and treated early. This case highlights the diagnostic challenge posed by SLE. Because patients may present to an ophthalmology clinic with ocular findings, ophthalmologists must seek out systemic symptoms and maintain a high degree of clinical suspicion to avoid delays in diagnosis.

      Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this article.

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