SS is a rare disease characterized by cerebellar dysfunction, hearing loss, and spastic paresis. Other symptoms can be dysphagia, bladder disturbance, dementia, anisocoria, and anosmia. Besides, cerebellar ataxia and deafness occur in 90% of cases (4). In our study, both patients presented with signs of cerebellar dysfunction, gait imbalance, progressive sensorineural hearing loss, and dementia. SS is mostly caused by chronic or recurrent bleeding. The most common causes of bleeding are head or neck trauma, AVM, CNS tumors, previously CNS surgery, brachial plexus injury, and other cause of subarachnoid hemorrhage. Moreover, cerebral amyloid angiopathy is a cause of SS in older individuals. However, about 35% of SS cases are idiopathic (5, 6). As in our study, the cause of bleeding in both patients was not identified. Both patients did not have a history of previous trauma, and they never exhibited any intense intracranial hemorrhage symptoms. Table 1 shows clinical characteristics of reported cases of idiopathic SS (7-14).
Table 1: Clinical characteristics of reported cases of idiopathic SS
|
Author
|
Gender
|
Age (years)
|
Duration (years)
|
Reported symptoms
|
|
Chen et al
|
Male
|
62
|
1.5
|
Slurred speech and ataxia
|
|
Stabile et al
|
Male
|
45
|
8
|
Progressive gait difficulties, tinnitus and emotional liability
|
|
Vale et al
|
Male
|
49
|
6
|
Cerebellar ataxia, bilateral auditory loss, mild cognitive impairment
|
|
Matsuyama et al
|
Male
|
59
|
4
|
Cerebellar ataxia, hearing loss and disturbance of memory
|
|
Posti et al
|
1 Female
1 Male
|
F: 66
M: 59
|
F: 1
M:1
|
F: Severe headache, photophobia, meningismus, and nausea
M:Unconsciousness and hemiparesis
|
|
Nakane et al
|
Female
|
57
|
Not reported
|
Sensorineural hearing impairment, cerebellar ataxia, pyramidal tract signs, dysarthria, and neurogenic bladder
|
|
Phanthumchinda et al
|
Male
|
58
|
5
|
Chronic progressive hearing loss and gait instability
|
|
Kresojević et al
|
Female
|
71
|
7
|
Progressive bilateral hearing loss, unsteady gate, hand clumsiness and dysarthria
|
The mechanism of SS is still unknown; however, the breakdown of erythrocytes or red blood cells from blood results in lysing and hemosiderin release. In reaction to this increase in heme levels, heme oxygenase-I enzyme is released by Bergmann glia and microglia cells, which splits the free heme into biliverdin, carbon monoxide iron (15, 16). The deposition of hemosiderin is associated with demyelination, gliosis, and neuronal loss. Sensorineural hearing loss is the most common symptom of SS that leads to complete deafness in 1 to 12 years (17). In our study, the first case developed complete deafness after twelve years at the age of thirty-five.
The diagnosis of SS was based on autopsies and biopsies before the use of neuroimaging. SS can also be diagnosed by cerebrospinal fluid (CSF) examination through xanthochromia, elevated presence of red blood cells (RBCs), high iron and ferritin concentrations, and elevated levels of the proteins Tau, beta-amyloid (Ab42), and glial fibrillary acidic protein (GFAP), but in most of the cases CSF is normal (18). CT scan of SS patients shows high signal rims and/or atrophy. SS-CNS is currently diagnosed by MR images demonstrating pathological findings caused by iron deposition beneath the surface of CSF in CNS tissues (7). The characteristic pathological finding is the existence of a signal loss on the surface of the CNS structures on a T2-weighted image. Cerebellar atrophy, spinal cord atrophy, and hyperintense rime can also be seen. Susceptibility-weighted imaging (SWI) is a new MR sequence that exhibits extreme sensitivity to blood-degradation products i.e. iron and hemosiderin. For the first time in Iran, SPECT for Tc-99m labeled RBC for detecting hemosiderin was performed in both patients but revealed nothing in favor of occult bleeding source. Finally, in our study, both patients underwent SWI MRI, and SS were confirmed based on MRI findings (1, 15, 19).
SS is a progressive neurological condition that must be identified early in order to be successfully treated. Studies have indicated that the first presentation usually appears after at least six months of subarachnoid hemorrhage from injury in 97% of cases (17, 20). While, the source of bleeding in most of the cases is evident. When the source of hemorrhage is detected in MRI, the purpose of treatment should be to discourage the disease's worsening by eliminating the source of subarachnoid hemorrhage surgically. Unfortunately, there is no treatment to reverse the hemosiderin deposition damaging effects (21). The most common therapy is iron chelators, such as deferiprone and desferrioxamine. Among iron chelators, deferiprone can cross the blood-brain-barrier to chelate the hemosiderin in the CNS (6). In a clinical trial by Levy et al, ten patients with SS were treated with deferiprone, and after 90 days of treatment, four patients revealed hemosiderin deposition decrease on MRI (22). Another study by Kessler et al on 38 patients with SS demonstrated a measurable reduction in hemosiderin by MRI in half of patients after two years of follow up. Also, the safety profile of deferiprone was confirmed (23). Although, most of the reported cases did not report significant improvement in symptoms or halting the disease progression using iron chelators (20). In our study, case 1 indicated the complete recovery of cognitive function and improvement of other symptoms to a certain extent. But, case 2 represented modest recovery in gait disturbance, ataxia, and hearing loss. However, none of patients had reduction in hemosiderin in their follow up brain MRI.
In conclusion, SS is a rare CNS disorder caused by hemosiderin deposition in the leptomeninges, subpial layer, ependymal surface and can result in neurological dysfunction and progressive, irreversible signs and symptoms. Here, we presented two cases of SS with severe symptoms that were misdiagnosed. To prevent potential misdiagnoses, we recommend that SS should be considered as a clinical diagnosis for elderly patients, particularly those on anticoagulation or with or without a history of brain damage or accident, which have bilateral sensorineural hearing loss and gait ataxia.