Cerebrospinal fluid biomarkers of superficial siderosis in patients with spontaneous intracranial hypotension

Abstract

Background and purpose Spontaneous intracranial hypotension (SIH) is an important etiology of infratentorial superficial siderosis (iSS) of the central nervous system. However, the prevalence of iSS amongst patients with SIH is unknown and the imaging findings of iSS might represent a late stage of disease. The aim was to identify cerebrospinal fluid (CSF) biomarkers of iSS in patients with SIH. Methods Consecutive patients evaluated for SIH at our institution between May 2017 and January 2019 were included. Lumbar CSF samples were analyzed for the presence of ferritin and bilirubin. Magnetic resonance imaging was assessed for the presence of iSS. Results Twenty‐four patients with SIH were included. CSF samples were positive for bilirubin in 2/19 (10.5%). CSF ferritin was elevated in 7/23 (30.4%). Signs of iSS on imaging were present in four patients (16.7%). All patients with imaging signs of iSS demonstrated elevated CSF ferritin. Ferritin level was significantly higher amongst patients demonstrating iSS compared to those without (median 45.0 vs. 11.0 μg/l; p = 0.003). Symptom duration was longer in patients with iSS than in patients without iSS (median 40 months vs. 9 months, p = 0.018). Conclusion Cerebrospinal fluid alterations indicative of iSS are prevalent amongst patients with SIH. It is speculated that a preclinical phase without symptoms or imaging signs but during which elevated biomarkers of the disease are apparent from CSF analysis might exist. It is suggested that measurement of CSF ferritin is incorporated in the work‐up of patients with SIH to identify those at risk of developing iSS.

Progressive superficial siderosis despite complete remission of intracranial hypotension symptoms following epidural patching: Case report

“…7,9 Both CSF xanthochromia and MRI-detected hemosiderin serve as markers for ongoing and past bleeding, respectively, and recent data suggest CSF ferritin may also prove useful for identifying patients at risk of developing superficial siderosis. 10 At the time of surgical repair, the dura at the site of ventral spinal dural defects has been reported to directly give rise to slow subarachnoid bleeding from friable dural and epidural veins, 11,12 and arteries 13 at the dural defect itself, as well as from veins bridging the epidural collections. 14 Thus, evidence predominantly supports a ventral spinal dural origin of the bleeding.…”

“…The progression from a long prodromal symptom‐free phase to irreversible neurodegeneration underscores the importance of early detection and intervention 7,9 . Both CSF xanthochromia and MRI‐detected hemosiderin serve as markers for ongoing and past bleeding, respectively, and recent data suggest CSF ferritin may also prove useful for identifying patients at risk of developing superficial siderosis 10 …”

Superficial siderosis of the central nervous system mimicking degenerative cerebellar ataxia

“…There is also a lack of body uid biomarkers. Hani et al reported that CSF ferritin was elevated in patients with spontaneous intracranial hypotension, who were potentially at risk of developing super cial siderosis [11] . The present case showed that serum ferritin was signi cantly higher than normal level.…”

Non-invasive biomarkers for spontaneous intracranial hypotension (SIH) through phase-contrast MRI

“…Other symptoms comprise audiovestibular deficits, visual disturbances, nausea, and cognitive decline, among an array of many other complaints [ 7 ]. The clinical presentation can appear inconsistent or even paradoxical, posing diagnostic challenges [ 8 ], and the patient at risk of chronic subdural hematoma [ 9 – 12 ], bibrachial amyotrophy [ 13 ], mimics of fronto-temporal dementia [ 14 – 16 ], and deficits caused by superficial siderosis [ 13 , 17 – 19 ].…”