Superficial siderosis: A rare occurrence in children.

Superficial siderosis of the central nervous system results from deposition of hemosiderin in the subpial layers of the brain and spinal cord. Patients usually present after 40 years of age with progressive ataxia and sensorineural hearing impairment. We present the case of a twelve-year-old boy who had a surgery of the posterior fossa at the age of two years and then developed recurrent headaches, instability of gait, and hearing deficit at around ten years of age. Clinical examination revealed progressive ataxia and mild sensorineural hearing loss. He also had infrequent seizures with mild electroencephalographic abnormality. His serial magnetic resonance imaging (MRIs) showed a progressive deposition of hemosiderin in the cerebellar folia and around the brainstem, confirming a diagnosis of superficial siderosis. This case report draws attention to this rare condition, usually seen in adults, even though rarely it can be seen in children as a chronic sequela of surgery of the posterior fossa.

Introduction

Superficial siderosis of the central nervous system due to chronic, recurrent subarachnoid hemorrhage is a rare and potentially debilitating disorder. The classic manifestation is progressive bilateral sensorineural hearing loss, although ataxia and pyramidal signs also are common.[1] In the largest review of literature to date, 87 cases of superficial siderosis have been mentioned to be reported in the world.[2] Though the age of presentation ranges from 15 to 78 years, it is seen more commonly in patients above 40 years. Almost all the published cases are those seen in adults. We hereby present a young boy with this disorder to emphasize its occurrence in children.

Case Report

A twelve-year-old boy presented to the neurology outpatient clinic with a history of intermittent holocranial headaches since two years and recent-onset blanking spells. The headaches were moderately severe, with no diurnal variation, occurring once in two weeks with no particular aggravating factor and subsiding with analgesic medication. He had a normal birth and early development. However, at two years of age, he had developed sudden-onset vomiting, irritability, and imbalance which was progressive, not associated with fever, trauma, or varicella infection. Over the subsequent month, he developed a divergent squint. A computed tomography of the brain revealed a mass lesion in the cerebellar vermis with supratentorial hydrocephalus. He underwent near-total excision of the tumor, with a thin rim of the tumor left behind. The histopathology of the tumor revealed medulloblastoma. For the residual rim of tumor margin, he was subjected to external radiotherapy to the posterior fossa with 6 MV photons (total dose being 5040cGy/28Fr/54 days) and was declared free of the disease subsequently. He was asymptomatic till the age of 10 years when he developed the headaches. A magnetic resonance imaging (MRI) of the brain was done which was normal except for postoperative changes; hence, the headaches were treated with plain analgesics. Over the next two years, he developed intermittent brief episodes of blanking spells, when he was referred to our center. On examination, his mini-mental state examination score was 28/30. A thorough neurological assessment revealed nystagmus, ataxia, and dysarthria with a normal tone. Deep tendon reflexes were pendular with flexor plantars. An electroencephalogram done for the blanking spells showed mild epileptiform abnormality and he was put on oxcarbamazepine. He was lost to follow-up for the next two years. Then he had a flurry of seizures and was admitted to our hospital. This time on examination, his dysarthria and ataxia had clearly worsened. His mini-mental state examination score had dropped to 22/30. He had acquired mild hearing impairment. A repeat MRI revealed cystic space in the posterior fossa (as a result of the previous surgery) and hypointensities around the cerebellar folia [Figure 1a]. This was confirmed to be hemosiderin on the susceptibility weighted images. Assessment of brainstem auditory evoked potentials confirmed bilateral mild sensorineural hearing loss. A repeat clinical assessment after six months showed significant deterioration in dysarthria and ataxia. A repeat MRI after six months showed progression in the deposition of hemosiderin in the cerebellar folia from the previous one [Figure 1b]. The clinical picture of a progressive worsening ataxia with sensorineural hearing loss along with the neuroimaging findings of the deposition of hemosiderin in the cerebellum clinches a diagnosis of superficial siderosis in this child, secondary to the surgery of the posterior fossa done in early childhood.

Figure 1

(a) Susceptibility weighted images showing hypointensities around the cerebellar folia, representing deposition of hemosiderin (b) Imaging done after six months showed progressively increased deposition of hemosiderin

Discussion

Superficial siderosis of the central nervous system was first described in 1908. There were several publications on its pathogenesis and clinical manifestations during the 1960s.[34] Nevertheless, the origin of superficial siderosis of the central nervous system remains undetermined in most cases. Highly vascular spinal tumors, vascular abnormalities of the central nervous system, and surgical procedures of the posterior fossa are the most commonly identified sources of chronic bleeding.[56] A past history of trauma and prior intradural surgery may be further risk factors. It is a distinct clinical syndrome characterized by sensorineural deafness (95%), cerebellar ataxia (88%), and pyramidal signs (76%). Other features include dementia (24%), bladder disturbance (24%), anosmia (at least 17%), anisocoria (at least 10%), and sensory signs (13%). Less frequent features are extraocular motor palsies, pain in the neck or back, bilateral sciatica, and lower motor neuron signs (5-10% each).[2] In a case report by Sevki et al., headache was also quoted to be a presenting symptom.[7] In our patient, headache was the main presenting complaint followed later by progressive ataxia and hearing loss.

The pathogenesis of superficial siderosis involves recurrent subarachnoid hemorrhage resulting in the prolonged contact of these tissues with iron.[89] Within the cerebellum, the microglia as well as Bergmann glia are uniquely sensitive to iron-mediated cell damage. The terminal processes of Bergmann glia that interface with the subarachnoid space mediate iron uptake from the cerebrospinal fluid (CSF), inducing the synthesis of ferritin within these cells. Because ferritin sequesters iron and is thus thought to play a role in iron detoxification, intracellular iron may not cause toxicity until ferritin biosynthesis is overwhelmed by a large iron load. Excess free iron may then stimulate lipid peroxidation, leading to localized tissue necrosis.

In the past, superficial siderosis was diagnosed almost exclusively at autopsy. With the advent of MR imaging, the diagnosis has been made increasingly premortem. MRI has identified siderosis in reportedly asymptomatic patients. In one series, which examined 8,843 consecutive MRI studies, 0.15% of the patients had MRI findings consistent with superficial siderosis. Eighty-five percent of these patients reported no symptoms.[10] In our patient, his early ataxia was attributed to his surgery. However, he had clear signs of a progressive deficit on serial assessments.

In most cases, treatment is limited to being symptomatic. The use of various therapies has been reported without a clearly discernible benefit, namely, steroids, iron chelators, selegiline, vitamin C, and other antioxidants. In cases where a source of chronic subarachnoid bleeding is identified, definite management should be aimed at stopping the bleeding by surgical or endovascular intervention. However, in about 25-40% of the patients, a source of siderosis is not identified, as in our patient, and treatment remains essentially symptomatic.

To conclude, our case is unusual as the classical syndrome of superficial siderosis is seen at a young age, secondary to an early surgery of the posterior fossa.