Study: Refractory Headache in Children With SLE Could Be a Sign of Intracranial Hypertension

Clinicians should be vigilant and perform neurological and ophthalmological examinations in patients with persistent headaches, the authors said.

Patients with systemic lupus erythematosus (SLE) with refractory headache warrant further evaluation—particularly if they are children—in order to rule out treatable ailments such as intracranial hypertension, according to a new review and case series published in Pediatric Rheumatology.

Central nervous system involvement is a common feature of SLE, often characterized by neuropsychiatric features, such as headache, cognitive dysfunction, and cerebrovascular disease, reported corresponding author Cuoghi Edens, MD, of University of Chicago Medicine and colleagues. However, despite the prevalence of those symptoms among patients with neuropsychiatric SLE, those symptoms are not currently included in the American College of Rheumatology’s classification criteria, the investigators noted.fha

One potential cause of refractory headache is intracranial hypertension, also known as pseudotumor cerebri (PTC), or pseudotumor cerebri syndrome (PTCS). PTCS has been reported in children and adults with SLE, although Edens and colleagues said there is not yet evidence to validate a direct association between SLE and PTC. In their new report, the investigators discussed 8 cases in which children with neuropsychiatric SLE experienced intracranial hypertension and sought care at University of Chicago Medicine. The authors said they hope to emphasize the importance of performing neurologic and ophthalmologic evaluations in patients with SLE and refractory headaches.

The patients ranged in age from 11 to 14 years at SLE diagnosis. However, one patient was diagnosed with PTCS a year before her SLE diagnosis (age 10), and 3 patients were 16 years old before they were diagnosed with PTCS. Five of the 8 patients had a lengthy experience with headaches, lasting at least 9 months and requiring multiple admissions to the hospital.

All 8 of the patients had SLE that was classified as severe at the time of their diagnosis of PTCS, based on the SLE Disease Activity Index, the investigators said.

“Regarding serologic findings, 4 of 8 patients had positive antiphospholipid antibodies, 7 of 8 patients had low complement levels, and 6 of 8 patients had elevated inflammation markers. Seven of 8 patients had lupus nephritis, with 6 of 8 having class V lupus nephritis,” the authors said.

A majority of the patients (5) were obese, based on body mass index. All of the patients had normal renal function, but 3 had nephrotic range proteinuria and low serum albumin levels, the investigators said. Half of the patients had abnormal neurological examinations, but only 1 patient had abnormal cerebrospinal fluid (CSF) composition, they said.

“Although the first CSF opening pressure was borderline in 3 of 8 patients, the diagnosis was explicitly supported in those patients by failing other measures to alleviate their refractory [headache], including controlling the underlying active lupus disease and remarkable improvement after therapeutic [lumbar puncture; LP] and acetazolamide treatment,” Edens and colleagues wrote. Optic nerve examination showed papilledema in 3 patients.

The primary treatment used for the patients was acetazolamide. Two of the patients were able to cease taking the drug without a return of the headaches.

The investigators conceded that it can be difficult to know how to approach chronic headaches in patients with SLE, due to the wide range of potential causes, and the fact that headaches are common in the general population. However, they said it is important for physicians to catch PTCS early, as it can lead to vision loss if left untreated.

“Proper evaluation of intracranial hypertension through complete neurologic examination, ophthalmological examination, neuroimaging, and [lumbar puncture] with opening pressure should be pursued in any SLE patient with a refractory [headache] or sixth nerve palsy,” Edens and colleagues wrote.

They said lupus nephritis, active disease, and corticosteroid use could be factors that increase the likelihood of PTCS. Patients should be given regular fundus examinations during follow-up visits, the authors added, since this can help detect even asymptomatic intracranial hypertension. If PTCS is diagnosed, therapeutic lumbar puncture and acetazolamide are typically successful treatments, they concluded.


Moussa T, Abdelhak M, Edens C. Pseudotumor cerebri syndrome in children with systemic lupus erythematosus: case series and review. Pediatr Rheumatol Online J. Published online April 15, 2022. doi:10.1186/s12969-022-00688-5

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