The Acute Superficial Siderosis Syndrome — Clinical Entity, Imaging Findings, and Histopathology

Abstract

Superficial siderosis is a consequence of repetitive bleeding into the subarachnoid space, leading to toxic iron and hemosiderin deposits on the surface of the brain and spine. The clinical and radiological phenotypes of superficial siderosis are known to manifest over long time intervals. In contrast, this study defines the “acute superficial siderosis syndrome” and illustrates typical imaging and histopathological findings of this entity. We describe the case of a 61-year-old male patient who was diagnosed with a melanoma metastasis in the right frontal cortex in February 2019. Within a few weeks he developed a progressive syndrome characterized by cerebellar ataxia, gait disturbance, signs of myelopathy, and radiculopathy. MRI revealed ongoing hemorrhage from the metastasis into the lateral ventricle and the subarachnoid space. A semiquantitative assessment of three subsequent MRI within an 8-week period documented the rapid development of superficial siderosis along the surface of the cerebellum, the brain stem, and the lower parts of the supratentorial regions on T2*-weighted sequences. The diagnosis of a superficial siderosis was histopathologically confirmed by identifying iron and hemosiderin deposits on the cortex along with astrogliosis. The recognition of this “acute superficial siderosis syndrome” triggered surgical removal of the hemorrhagic metastasis. Based on a single case presentation, we define the “acute superficial siderosis syndrome” as a clinical entity and describe the radiological and histopathological characteristics of this entity. Early recognition of this syndrome may allow timely elimination of the bleeding source, in order to prevent further clinical deterioration.

Infratentorial Superficial Siderosis and Spontaneous Intracranial Hypotension

“…Except for one patient in whom iSS was detected on MRI within weeks of SIH symptom onset, 31 the iSS did not develop within the first year of SIH symptom onset in any other patient and frequency of iSS increased exponentially with time elapsed from the onset of SIH symptoms, not reaching a clear plateau phase. The development of SS over a short period of time is rare but has been reported previously and has been called “the acute superficial siderosis syndrome.” 32 In a prior study of the risk of developing iSS in patients with persistent ventral spinal CSF leaks, we only included patients who were seen within 1 year of SIH symptom onset to minimize ascertainment bias 14 . Comparing the rate of developing iSS over time in that study to the present study, we found no statistically significant difference, providing internal validity to our estimates of developing iSS for the other types of spinal CSF leaks as well.…”

“…The development of SS over a short period of time is rare but has been reported previously and has been called "the acute superficial siderosis syndrome." 32 In a prior study of the risk of developing iSS in patients with persistent ventral spinal CSF leaks, we only included patients who were seen within 1 year of SIH symptom onset to minimize ascertainment bias. 14 Comparing the rate of developing iSS over time in that study to the present study, we found no statistically significant difference, providing internal validity to our estimates of developing iSS for the other types of spinal CSF leaks as well.…”

Headache persisting after aneurysmal subarachnoid hemorrhage: A narrative review of pathophysiology and therapeutic strategies

“…Oxidative damage to cells in the central nervous system (CNS) is a common and often irreversible consequence of SAH due to factors such as free hemoglobin and resulting reactive oxygen species from superficial siderosis, and may play a role in headache etiology through inflammation and neuronal dysfunction 35 . In addition to contributing to the inflammatory processes mentioned in the preceding paragraph, superficial siderosis represents a long‐term change to brain parenchyma that is radiographically detectable after certain cases of SAH and has been postulated itself to cause neurologic disorders 36,37 . Siderosis has not been studied with regards to post‐SAH headache; however, involvement of dural or trigeminal nociceptive receptors or parenchymal changes resulting in cortical spreading depolarizations (CSDs) may be feasible pathways by which siderosis could lead to post‐SAH headache.…”

“…35 In addition to contributing to the inflammatory processes mentioned in the preceding paragraph, superficial siderosis represents a long-term change to brain parenchyma that is radiographically detectable after certain cases of SAH and has been postulated itself to cause neurologic disorders. 36,37 Siderosis has not been studied with regards to post-SAH headache; however, involvement of dural or trigeminal nociceptive receptors or parenchymal changes resulting in cortical spreading depolarizations (CSDs) may be feasible pathways by which siderosis could lead to post-SAH headache. Removal of residual blood from the subarachnoid space through large volume lumbar punctures has been postulated to improve headache pain after SAH through decreased meningeal irritation and inflammation, and an ongoing clinical trial (the SAH-HELP trial, NCT03754335) will soon provide results concerning any benefit on headache in this population.…”

Cerebral Superficial Siderosis

“…Chronic ongoing or repetitive low-volume bleeding in the subarachnoid space can occur before the diagnostic conformation of a CNS tumor (see Fig. 2 ; [ 11 ]) or may be due to postoperative residual tumor tissue or a postsurgical cavity. There is evidence that AVMs found in the diagnostic work-up of SS are often incidental [ 8 ].…”