A 15-year-old girl is fatigued, flushed, and cannot remember anything. She went from As to Fs in school and was seen by her mother putting groceries away in her clothing drawer.
A 12-year-old boy had his appendix out last week. Now he is behaving oddly and his parents have brought him to the emergency room (ER) because he won’t stop swearing—and he undresses in public.
A 15-year-old boy with lupus suddenly has a grand mal seizure. CT of the brain shows a large stroke.
A 17-year-old girl recently diagnosed with lupus nephritis presents to the ER after a bout of diarrhea because her “legs won’t work.” She is admitted to the hospital for the treatment of acute inflammatory demyelinating polyneuropathy.
All of these children presented with dramatic and serious clinical findings and were subsequently diagnosed with neuropsychiatric systemic lupus erythematosus (NPSLE). NPSLE is arguably the least understood manifestation of SLE, as it is associated with a complicated and often baffling range of clinical presentations.1 Since the publication of the new ACR Case Definitions for NPSLE,2 studies have confirmed the presence of NPSLE in as many as 80% of adults with SLE.3 NPSLE syndromes range from diffuse central nervous system (CNS) disorders (e.g., acute confusional state, psychosis, anxiety, and depressive disorders), including cognitive dysfunction, to focal CNS syndromes (e.g., seizures, cerebrovascular disease, chorea, myelopathy, transverse myelitis, demyelinating syndrome, aseptic meningitis, and headaches) and peripheral nervous system disorders (e.g., neuropathies and acute inflammatory demyelination).2
The most common NPSLE symptoms are headache and neurocognitive dysfunction.4 The latter may be transitory or persistent over years and can occur in patients without overt NPSLE or even systemic disease activity. Although risk factors for neuropsychiatric disease are not well defined, a longitudinal study of 123 multiethnic adults with SLE (SALUD study) suggests that a higher level of depression is associated with neurocognitive dysfunction, although the cause and effect of this relationship remains unclear. Furthermore, persistent prednisone use, the presence of antiphospholipid antibodies, a lower education level, and diabetes are associated with cognitive decline in adults with SLE.5
Neuropsychiatric involvement may occur even more commonly in children than in adults with SLE, with up to 95% of the pediatric patients manifesting at least one symptom of NPSLE in some studies.3,6 Often, NPSLE develops early in the disease course, and up to 25% of the patients manifest symptoms within 30 days of diagnosis.7 Cognitive impairment from NPSLE can affect any or all of the following cognitive functions: simple or complex attention, reasoning, executive skills (e.g., planning, organizing, sequencing), memory (e.g., learning, recall), visual-spatial processing, language (e.g., verbal fluency), and psychomotor speed. The severity of cognitive dysfunction in NPSLE ranges from mild impairment to severe dementia. This situation may not be unique to children with lupus, however, because neurocognitive dysfunction occurs with other chronic pediatric diseases, including early-onset insulin-dependent diabetes and sickle cell anemia, and following treatment for childhood malignancies.