Superficial siderosis is a rare pathological condition that leads to hemosiderin deposition in the leptomeninges with possible neurological deficits.
On MRI, it classically looks like a low-intensity rim over the brain or spinal cord surface, which is visible on gradient echo sequences or SWI sequences.
Superficial siderosis is a syndrome associated with the deposition of iron metabolites. Prolonged exposure of hemosiderin to brain cells, especially microglia and oligodendrocytes, leads to ferritin production, which aggravates the disease. The cells that produce ferritin most actively are in the cerebellum, which explains why superficial siderosis manifests itself there in the first place.
Hemosiderin is a water-insoluble derivative of ferritin with a higher concentration of iron (the ferritin molecule contains 20% iron, while hemosiderin contains more than 25-30% iron). According to its chemical structure, hemosiderin is a colloidal iron hydroxide combined with mucoproteins of the cell. Ferritin is a water-soluble form of the iron depot, a protein that reversibly binds and stores iron molecules. One ferritin molecule binds up to 2500 iron atoms in a complex of hydroxides and phosphates. At the same time, ferritin protects the body from the toxic effects of iron, keeping it in an oxidized trivalent state, unable to catalyze the production of free radicals. Immunologically, hemosiderin is identical to ferritin.
At the moment, there is a distinction between idiopathic and symptomatic siderosis. The causes of hemorrhage leading to the development of symptomatic may be:
- CNS tumors (21%)
- neurotrauma (13%)
- arteriovenous malformations/aneurysms (9%)
- neurosurgical interventions (7%)
- brachial plexus injuries (6%)
- cerebral amyloid angiopathy (3%)
- chronic subdural hematoma.
In a third of cases, despite a thorough examination, the cause of the cortical superficial cannot be established, and then we are talking about idiopathic superficial siderosis.
Superficial siderosis is thought to result from multiple recurrent subarachnoid hemorrhages, although hemorrhages are not always visualized radiologically. Although small deposits of hemosiderin can be visible along the margin of previous hemorrhages or the surgical site, a single episode of hemorrhage is usually not enough to develop superficial siderosis.
Damage to the 8th pair of cranial nerves, leading to sensorineural hearing loss, is believed to be due to a combination of several factors of the lengthy course of the nerve in the cistern (which is the subarachnoid space), the susceptibility of microglial cells (which play a role in myelination) to damage to iron-containing substances.
Clinical manifestations directly depend on the localization of hemosiderin deposits. Typical symptoms include:
- sensorineural hearing loss occurs in 95% of cases, bilateral and progressive
- cerebellar ataxia 90%
- pyramidal symptoms 75%
- urinary incontinence
- disorders of the cranial nerves
- sensory deficits
- cognitive impairment
It is important to remember that the degree of lesion on imaging does not always correlate with the degree of clinical presentation.
Etiology. Repeated subarachnoid hemorrhages are the cause in 50% of cases.
- defects in the dura mater of the spinal cord:
- traumatic avulsion of the nerve roots of the cervical spine
- defects of the hard shell with an accumulation of cerebrospinal fluid
- postoperative pseudomeningocele
- intracranial neoplasms:
- small ependymoma
- vascular abnormalities
- arteriovenous malformations
- cerebral amyloid angiopathy – in 60% of patients
- idiopathic superficial siderosis – in 40% of cases
Diagnosis and treatment
For a long time, superficial siderosis was diagnosed only by visual examination of the brain substance during biopsy or surgical interventions. It is also identifiable as a postmortem finding during pathomorphological examination. The criteria for the diagnosis 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.
Currently, non-invasive diagnostics is possible through magnetic resonance imaging (MRI) use. MRI diagnostics is necessary in case of suspicion of superficial siderosis in the early stages. The brain MRI must be pathognomonic and allow identifying the presymptomatic phase of the disease. The criteria in MRI are linear hypointense areas on the surface of the cerebellum, brain stem, lower hemispheres, around the VIII pair of cranial nerves, and on the surface of the spinal cord. A characteristic is a cerebellar atrophy, especially in the vermis and anterior cerebellar hemispheres. At the same time, hemosiderin deposits on MRI of the brain are determined much earlier than signs of atrophy of the medulla.
MRI is the method of choice for detecting superficial siderosis. Signs of a very specific pia mater and ependymal surface due to accumulations of hemosiderin have a low signal intensity, especially in the region of the brain stem and cerebellum (the worm and cerebellar lamellae are the best places for detecting deposits). In old cases, cerebellar atrophy may be observed.
- T2: decrease in intensity
- T1: decrease in intensity
- T2 *: decrease in signal intensity up to its loss
- SWI: Decrease signal intensity up to dropout
As part of the superficial cortical protocol, if they identify no intracranial pathology, it is necessary to examine the entire spinal canal.
Treatment and prognosis. Unfortunately, there is no proven therapeutic regimen for superficial siderosis; therefore, clinical examination aims to identify the cause, although this is often not possible. Iron chelating agents have had limited treatment efficacy.
When the cause of superficial siderosis is not corrected, slow progression is observed.
- Idiopathic superficial siderosis is a chronic, slowly progressive neurodegenerative disease associated with the deposition of hemosiderin in the pia mater. With it, there is the likelihood of developing a rather severe neurological deficit. The disease develops much more often in men than in women. The first symptoms of superficial siderosis appear between the ages of 14 and 77. Life expectancy from the onset of the disease ranges from 1 to 38 years. Most often, superficial siderosis develops after forty years and leads to progressive bilateral sensorineural hearing loss, mainly with the loss of high-frequency tones, cerebellar dysarthria, and ataxia. In addition, superficial siderosis can mimic various neurological and otorhinolaryngological diseases. Therefore, the clinician should make a differential diagnosis with anosmia, pyramidal disorders, myelopathy, dysfunction of the urinary system, frontotemporal dementia, as well as various cranial nerve palsies. Disabilities and difficulties in self-care develop after about 5 to 15 years.
- Cortical superficial siderosis has been recently described as another key hemorrhagic marker of cerebral amyloid angiopathy. This phenomenon is associated with repeated episodes of blood seepage into the subarachnoid space from the affected fragile vessels. Deposition of hemosiderin in the superficial layers of the cortex on each side of the gyrus is manifested by a characteristic pattern of signal dropout on T2 * and SWI MRI sequences in the form of two tracks.
A specific clinical manifestation of cortical superficial siderosis is transient focal neurological episodes, observed in 14% of patients.
Is superficial siderosis fatal?Superficial siderosis symptoms are fatal. If you consult a doctor in time and start treatment, you can prevent the progression of the disease.
How is superficial siderosis treated?Doctors currently do not have a cure for superficial siderosis. Oral chelating drugs are used, which can cross the blood-brain barrier to treat and stop the progression of the disease. Oral chelation therapy is risky, and doctors may not recommend it for all patients.