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Superficial siderosis of the CNS is a rare syndrome of progressive cerebellar ataxia and sensorineuronal deafness associated with haemosiderin deposition from chronic subarachnoid bleeding.1 We describe a patient with typical features of superficial siderosis and an anterior horn cell syndrome, a combination that to our knowledge has never been previously reported.
A 59 year old man presented with a 4 year progressive history of unsteadiness of gait, bilaterally impaired hearing, and weakness which had begun in the left hand, spreading to involve the left arm and leg, and right hand. He had a 2 year history of cerebellar dysarthria, bladder hesitancy with postmicturition dribbling, and impotence. Examination disclosed a broad based ataxic gait with left sided limb ataxia. Apart from bilateral sensorineuronal deafness the cranial nerves were normal. There were fasciculations in the arms and legs. In the upper limbs he had asymmetric wasting and weakness of the intrinsic hand muscles, biceps, and triceps bilaterally. In the left lower limb there was wasting and weakness of the hip flexors and quadriceps. Sensory examination was normal. The deep tendon reflexes were all present and symmetric. The abdominal reflexes were present and the plantar responses were flexor.
Magnetic resonance imaging of the brain and spinal cord demonstrated haemosiderin deposition around the cerebellar folia, outlining the whole spinal cord and sacral cul de sac (fig 1⇓). There were no other abnormalities on the MRI and a carotid and spinal angiogram failed to disclose a source of bleeding within the CNS. The patient declined a lumbar puncture to look for evidence of active haemorrhage. There was no history of CNS trauma or surgery.
Neurophysiological examination showed normal sensory nerve conduction. Motor conduction was essentially normal. Electromyography of the first dorsal interosseous and extensor digitorum communis muscles demonstrated fibrillations and fasciculations with high amplitude units. Somatosensory evoked potentials were normal from the arms but showed delayed latencies in the legs.
A diagnosis of superficial siderosis was made and he was given a trial of subcutaneous desferrioxamine fortnightly for 8 weeks with no benefit. The patient has continued to deteriorate.
Superficial siderosis of the CNS is a clinical syndrome characterised by progressive cerebellar ataxia and sensorineuronal deafness. Pyramidal signs develop in 76% and other features that may occur include dementia (24%), a neurogenic bladder (24%), anosmia (17%), aniscoria (10%), sensory signs (13%), and less frequent features are extraocular motor palsies, backache, sciatica, and lower motor neuron signs (all 5%–10%).1 Interestingly, in superficial siderosis the vestibulocerebellum is spared and so despite the central nature of the cerebellar syndrome nystagmus is commonly absent. The pathology of superficial siderosis is of haemosiderin deposits along the subpial surfaces of the CNS and is a consequence of chronic or recurrent bleeding into the subarachnoid space. Superficial siderosis has been reported as a consequence of surgery, aneurysms, vascular malformations, spinal tumours, and traumatic root avulsions. Often the source of the haemorrhage cannot be identified, even at necropsy.
Magnetic resonance scanning has enabled the diagnosis to be made in vivo. The characteristic finding is a rim of marked hypointensity on T2 weighted images surrounding the brain stem, spinal cord, sylvian and inter-hemispheric fissures, and a few cortical sulci. Occasionally the second and seventh cranial nerves are also involved. In addition to the marginal hypointensity created by the paramagnetic ferric ions, high signal in the adjacent cerebellar tissue, due to secondary gliosis, may be seen on T2 weighted MRI.2
The most striking and unique feature of the patient described was the extensive limb wasting and fasciculations with asymmetric weakness but preserved reflexes and an absence of sensory signs. These clinical findings, along with the neurophysiology, suggest an anterior horn cell pathology. In the review of Fearnley et al of 63 patients four had lower motor neuron involvement with absent or diminished reflexes thought to be secondary to arachnoiditis or radiculopathy. One patient had muscle wasting with brisk reflexes thought to be due to concurrent lower motor neuron pathology and myelopathy.1 In our patient the duration of the symptoms and the lack of bulbar and pyramidal features were against this being a classic amyotrophic lateral sclerosis. It is more likely that superficial siderosis was the cause of our patient's anterior horn cell dysfunction and it is recognised that iron pigmentation may be found deep within the spinal cord and intraneuronal deposits have been described.1 The clinical picture of anterior horn cell damage in superficial siderosis is of particular interest as in the review of Fearnley et al they note that although heavy haemosiderin deposition is recognised in the anterior horns of the spinal cord there is little in the way of neuronal fall out.
The predominance of CNS involvement and the paucity of lower motor neuron features in superficial siderosis has been the subject of several novel studies. Koeppen and Borke have shown that an intracisternal injection of red cells produces increased synthesis of ferritin in microglia, especially Bergmann glia in the cerebellum, and this binds with iron to form haemosiderin.3 It is postulated that the glia and astrocytes of the central nervous system respond to the presence of haemoglobin whereas this process does not occur in Schwann cells of the peripheral nervous system. This is supported by the pathological finding that there is a sharp demarcation of haemosiderin deposition in the cranial nerves and spinal roots at the junction of the central glial and peripheral Schwann cell segments. Koeppen and Detinger have also suggested that the formation of haemosiderin is neuroprotective and it is once this protection has been exhausted that tissue damage occurs, thus it is not the haemosiderin which is toxic but the unbound iron.4 There are no other case reports of superficial siderosis causing an anterior horn cell syndrome, posing the question of why our patient developed this combination. Whether our patient's presentation was due to anomalous intracellular processing or an unusual source of haemorrhage impacting on the spinal cord remains speculative. It is also possible that in our case the motor root exit zone is a site of iron deposition with resultant lower motor neuron pathology.
We think that our case of superficial siderosis with anterior horn cell dysfunction is unique, and raises interesting questions about pathological mechanisms in this rare disorder.