Superficial siderosis of the central nervous system is a syndrome associated with the deposition of iron metabolites, especially hemosiderin, in the pia mater and on the brain and spinal cord surface as a result of repeated hemorrhages of various etiologies and characterized by a chronic progressive course. Prolonged exposure of hemosiderin to brain cells, especially microglia and oligodendrocytes, leads to the production of ferritin, which aggravates the course of this disease. The cells most actively producing ferritin are located in the cerebellum (Bergman’s glia), and this explains why superficial siderosis is manifested there in the first place.

A case was described for the first time in 1908. At the moment, idiopathic and symptomatic siderosis is distinguished. The causes of hemorrhage leading to the development of superficial siderosis may be:

  • CNS tumors (21%)
  • neurotrauma (13%)
  • arteriovenous malformations/aneurysms (9%)
  • neurosurgical interventions (7%)
  • brachial plexus injuries (6%)
  • amyloid angiopathy (3%)
  • chronic subdural hematoma.

In a third of cases, despite a thorough examination, the cause cannot be established, meaning we are talking about idiopathic.

Diagnostics and treatment superficial siderosis

For a long time, this disease was diagnosed only by visual examination of the brain substance during surgery or biopsy. It was also identified as a postmortem finding during pathomorphological examination. The criteria for diagnosis and treatment of superficial siderosis in these cases is a change in the normal color of the brain matter in the form of deposits of brown pigment (hemosiderin) in the upper cortex and pia mater, most often in the cerebellum, brain stem, cranial nerves, and spinal cord. Often macroscopically, there are signs of repeated subarachnoid hemorrhages in the form of diffuse cerebral edema with small leptomeningeal blood clots. In addition, multiple petechial hemorrhages in both gray and white matter can be detected on brain slices.

Microscopic examination reveals thickening of the meninges, reactive gliosis and hemosiderin accumulations (subpial, subependymal), neuronal death, and signs of demyelination. Perivascular the spaces and walls of pial vessels are filled with macrophages containing hemosiderin, formed during the breakdown of hemoglobin and subsequent denaturation and deproteinization of the ferritin protein.

Modern methods of neuroimaging and health information, particularly magnetic resonance imaging, make it possible to carry out intravital and non-invasive verification of the diagnosis of superficial siderosis. And the widespread use of MRIs has led to a sharp increase in the number of detected cases of the described pathology.

In MRI, to detect hemosiderin deposits in the central nervous system, specialized modes are used sensitive to paramagnetic substances, such as hemosiderin and ferritin: T2-gradient echo and SWI. Signs of superficial siderosis on MRI are linear hypointense areas on the border of the brain substance, most pronounced on the surface of the cerebellum, brain stem the brain, the lower part of the hemispheres, around the VIII pair of cranial nerves, and on the surface of the spinal cord. Often, due to the lack of time with a large flow of patients, the high cost of an MRI scan, insufficient qualifications of a radiologist, and other factors, the scan area is limited only by the brain for its intended purpose.

Neurologists can help with diagnosis and treatment, as the main complaint of patients is progressive hearing loss and impaired gait. In the absence of possible causes of cerebral hemorrhages (signs of amyloid angiopathy, etc.), a doctor can diagnose idiopathic, and they may miss a possible source of superficial siderosis located in the spinal canal.

Pathogenesis

Pathogenesis

The classic causes of superficial siderosis are surgery and trauma. Other causes include the neoplastic process with ongoing hemorrhage, vascular malformations, and venous occlusion, and recurrent subarachnoid hemorrhages of small volume are also possible. The cortical form in older patients is most often associated with cerebral amyloid angiopathy. Acceleration of the synthesis of cerebellar ferritin and chronic intrathecal hemorrhages change the ability of microglia to biosynthesize ferritin, resulting in its accumulation under the pia mater; this results in the formation of free radicals, lipid peroxidases, and neuronal degeneration. In the classical form, hemosiderin deposits occur in the sheets and vermis of the cerebellum, the brain stem, and the VIII pair of cranial nerves. The cortical form occurs in 60% of patients with cerebral amyloid angiopathy, but in rare cases with intracerebral hemorrhage, without the presence of cerebral amyloid angiopathy.

Macroscopically, brown-yellow and dark gray inlays are determined on the surface of the affected structures, located along the grooves and cranial nerves.

Epidemiology. The disease develops in a wide age range between 14 and 77 years; more often, these pathological processes develop in men in a ratio of M: F 3: 1. 

Clinical manifestations. Patients with the classic form slowly develop progressive ataxia, dysarthria, anosmia headaches, bilateral sensorineural hearing loss, and gradual development of dementia is also possible. Some patients develop progressive myelopathy with the development of hemiparesis, dysfunction of the bladder. Often, decades pass between the pathological processes that cause superficial siderosis and the development of symptoms. The average presymptomatic phase is about 15 years.

Radiation diagnostics of superficial siderosis. CT semiotics:

The images show cerebral and cerebellar atrophy, especially in posterior fossa structures with disproportionately large cerebellar grooves. The most common manifestation described above occurs in the brain stem. A specific manifestation is a moderately hyperdense signal on the surface of the affected structures due to iron deposition. Care must be taken not to mistake the hyperdense signal on the surface of the brain for an acute subarachnoid hemorrhage, usually located in the grooves and cisterns, and vice versa, not to miss it if present.

MRI semiotics:

  • T1: A hyperintense signal can be detected on the surface of the brain. Also, how atrophic changes in cerebral and cerebellar hemispheres are determined.
  • T2Flair: a hypointense signal is detected along the brain’s surface, spinal cord, and cranial nerves in the form of a linear structure, usually ≤ 2 mm wide.
  • T2 GRE: is a more sensitive mode in detecting hemosiderin than the T2 mode; a bright hypointense signal is observed along with the pia mater and in the adjacent subpial structures of the brain. The areas of the altered signal are measured as broader structures compared to the T2 model. It is also possible to identify deposits in the ependymal layer of the ventricles and choroid plexuses.
  • DWI: no areas of diffusion limitation are detected in the absence of subarachnoid hemorrhage at the time of examination
  • T1 + C: no signs of abnormal accumulation of contrast agent are detected.
  • Is superficial siderosis fatal?

    The symptoms and signs of superficial siderosis can be fatal. But if you start treatment on time and consult a doctor, the patient can prevent the progression of the disease.
  • How is superficial siderosis treated?

    There is currently no cure for superficial siderosis. The only drugs currently available for treatment are oral chelating drugs, which can cross the blood-brain barrier.
  • What causes siderosis?

    Superficial siderosis is a rare disease caused by hemosiderin deposits in the brain and spinal cord subpial layers. Deposition of hemosiderin is the result of repeated bleeding into the subarachnoid space.
  • What is slow progressing superficial siderosis?

    Superficial siderosis of the central nervous system occurs due to hemosiderin deposition in the subpial layers of the brain and spinal cord. A clinical history of subarachnoid hemorrhage is often absent. Patients have slowly progressive gait ataxia and sensorineural hearing impairment.