A 13-year old previously healthy Hispanic female presented with 1 week of nighttime fevers (Tmax 38.8 degrees Celcius orally), 3-4 days of occipital headache with blurry vision, and 1 day of neck pain. Initial vital signs were normal. She was afebrile and awake, alert, and oriented. Her physical exam was significant for grade IV papilledema on ophthalmologic exam. She otherwise had a normal neurologic exam, without meningeal signs. All other systems were normal. Her initial differential was most concerning for infectious, metabolic or neurologic causes. Initial laboratory studies showed leukopenia with a white blood cell count of 3.9k/cum (normal value 5-10 k/cum), normocytic, normochromic anemia (Hgb 10.4), and normal platelet count. Leukopenia was noted on 2 occasions but was not sustained and resolved prior to treatment. Her erythrocyte sedimentation rate (ESR) and C-Reactive protein (CRP) were normal. Her urinalysis was without proteinuria or hematuria. She had normal renal function, electrolytes, toxicology screening, thyroid studies, folate, and vitamin B12 levels. Initial head CT showed diffuse cerebral swelling without herniation. Follow up brain MRI/MRA with and without contrast showed “symmetric diffuse T2 hyperintensity on the white matter of both cerebral hemispheres, brainstem, corpus callosum and cerebellar white matter with mild cerebellar tonsillar ectopia and no mass or midline shift”. This was consistent with diffuse brain swelling secondary to acute leukoencephalopathy. Brain MRA without contrast was without abnormalities. A lumbar puncture was unable to be performed due to severity of cerebral edema.
During her hospitalization, multiple subspecialty services were consulted including neurosurgery, neurology, genetics, metabolism, infectious disease, ophthalmology, and rheumatology. Infectious studies were significant for positive EBV NA IgG, EA IgG, VCA IgG and negative VCA IgM, positive CMV IgG and IgM, and positive Mycoplasma IgG and IgM. Immunofluorescent antibody testing for mycoplasma pneumoniae IgM was negative. Arbovirus panel testing (which includes STL Encephalitis virus, California encephalitis virus, eastern equine virus, western equine virus) was sent twice and was inconclusive on both occasions due to specimen producing a “non-specific fluorescence”. Other infectious studies were negative including serum CMV PCR, EBV PCR, herpes simplex (HSV) virus type 1 and 2, Cryptococcus blood antigen, human Immunodeficiency virus (HIV) 1 and 2 antibody and antigen, influenza A/B, adenovirus, parainfluenza 1-4, chlamydia pneumoniae, bocavirus, coronavirus, RSV A/B, rhinovirus/enterovirus, metapneumovirus, Lyme disease serologies, Brucella IgM/IgG, and West Nile IgM/IgG. TB spot testing was negative. An extensive metabolic workup was done and results were normal, including serum amino acids, urine organic acids, lactate, pyruvate, very long chain fatty acids, lysosomal panel, carnitine, homocysteine, and CK. An MR spectroscopy was completed which showed “elevation of the glutamine/glutamate complex in short echo MRS in both the left frontal lobe and right basal ganglia” without “significant abnormal elevated lactate peaks in the white matter basal ganglia”. Her lab workup did not support a primary metabolic disorder.
She was managed medically for her cerebral edema with sodium supplementation for therapeutic hypernatremia and acetazolamide. She remained afebrile until day 4 of her hospitalization, however on hospital days 5, 6, and 7 she developed fevers. At this time, she was initiated on doxycycline for presumed mycoplasma infection due to positive IgG and IgM mycoplasma titers. On day 7 of her hospitalization she had acute deterioration and became unresponsive and obtunded, requiring emergent intubation. A repeat head CT done at that time showed stable cerebral edema without new changes or herniation. EEG was negative for seizure activity. She was successfully extubated to room air within 24 hours and remained stable throughout the remainder of her hospitalization.
Rheumatology was consulted on day 8 of her admission for concern for CNS vasculitis or other autoimmune etiologies. She had an initial rheumatologic workup that included ANA of <1:40 by immunofluorescence (IF), but elevated anti-dsDNA (82.2), low C3 (21) and low C4 (2). Antiphospholipid antibodies were significant for beta 2-glycoprotein IgA 7.0 (reference range being < 7.0), with beta-2 glycoprotein IgG and IgM negative, anti-cardiolipin antibodies negative, and lupus anticoagulant negative. The hypocomplementemia and positive anti-dsDNA antibody prompted further evaluation, specifically for SLE. Additional lab testing revealed positive Smith (>8), SSA (>8), SSB (1.2, reference range <1.0), RNP (2.1, reference range <1.0), Ribosomal P (>8) and neuronal (>400, reference range 0-54) antibodies. ANA was repeated and again noted to be <1:40 by IF. She was ultimately diagnosed with SLE with CNS involvement. At this point in her disease process she had no other apparent organ involvement or other SLE features.
She was started on treatment for SLE and received 5 days of IV methylprednisolone (1gm) in addition to IV cyclophosphamide (initial dose 500 mg/m2) and IV Rituximab (500 mg/m2). Repeat MRI prior to discharge showed stable cerebral edema and leukoencephalopathy (Figure 1). Her headaches subjectively improved with therapy, and repeat ophthalmologic exam showed improvement of papilledema from grade IV to grade II-III by time of discharge. She was discharged home on day 19 of hospitalization on prednisone 60mg daily, hydroxychloroquine, and acetazolamide, with the outpatient management plan of second Rituximab infusion and monthly cyclophosphamide infusions and with IV solumedrol pulse dose therapy.