Cerebrospinal Fluid Alzheimer's Disease Biomarkers in Isolated Supratentorial Cortical Superficial Siderosis.

We evaluated cerebrospinal fluid amyloid-ß 1-40 (Aß40), amyloid-ß 1-42 (Aß42), total and phosphorylated-tau (t-tau and p-tau) in patients with symptomatic isolated cortical supratentorial superficial siderosis (SS), by prospectively recruiting ten patients with SS in the absence of pre-existing cognitive dysfunction, and comparing biomarkers with lobar hematoma cerebral amyloid angiopathy patients (LH-CAA, n = 13), Alzheimer's disease patients (AD, n = 42), and controls (n = 16). Compared to controls, SS patients showed statistically significant higher t-tau (p = 0.019) and lower Aß42 (p = 0.0084). Compared to other groups, SS showed statistically significant lower t-tau, p-tau, and Aß40 compared to AD (p = 0.0063, p = 0.0004, and p = 0022, respectively), and higher p-tau compared to LH-CAA (p = 0.012).

Superficial siderosis of the central nervous system associated with incomplete dural closure following posterior fossa surgery: report of 3 cases.

This report reviews a series of 3 patients who developed superficial siderosis following posterior fossa operations in which dural closure was incomplete. In all 3 patients, revision surgery and complete duraplasty was performed to halt the progression of superficial siderosis. Following surgery, 2 patients experienced resolution of their CSF xanthochromia while 1 patient had reduced CSF xanthochromia. In this paper the authors also review the etiology, pathophysiology, diagnosis, and treatment of this condition. The authors suggest that posterior fossa dural patency and pseudomeningocele are risk factors for the latent development of superficial siderosis and recommend that revision duraplasty be performed in patients with posterior fossa pseudomeningoceles and superficial siderosis to prevent progression of the disease.

Superficial siderosis should be included in the differential diagnosis of motor neuron disease.

INTRODUCTION: Recent studies have revealed that some patients with superficial siderosis (SS) show evidence of an intraspinal fluid-filled collection on imaging. Some of these patients also show clinical and/or imaging features of craniospinal hypovolemia related to dural defects. We report a patient with SS whose clinical presentation was suggestive of motor neuron disease and whose history was remarkable for cerebrospinal fluid (CSF) hypovolemia. This report also reviews the literature on the relationship between SS, dural defects, and CSF hypovolemia. CASE REPORT: A 58-year-old left-handed man was evaluated for an 18-month history of progressive imbalance with limb muscle weakness, wasting, and fasciculations. Brain magnetic resonance imaging (MRI) studies were remarkable for evidence of SS and diffuse pachymeningeal enhancement similar to that seen in craniospinal hypovolemia. Spine MRI showed a longitudinal intraspinal fluid-filled collection. A dynamic computed tomographic myelogram of the spine showed a CSF leak adjacent to a peripherally calcified disk at the T2-3 level. Following repair of the dural defect the patient noted an improvement in balance and strength and resolution of the fasciculations. A cervical and thoracic spine MRI showed resolution of the intraspinal fluid-filled collection, and a CSF study showed no red blood cells or xanthochromia. CONCLUSIONS: The clinical spectrum of disorders related to dural defects includes craniospinal hypovolemia, SS-related ataxia and impaired hearing, segmental weakness and atrophy with or without hyperreflexia, and spinal cord herniation. The clinical features of these conditions may overlap. Longitudinally extensive ventral dissecting meningoceles can be seen in all these conditions. A dynamic computed tomographic myelogram can identify a dural defect. In some cases the dural defect may result from an osteophyte.

CSF tau protein is a useful marker for effective treatment of superficial siderosis of the central nervous system: two case reports.

We report two cases of superficial siderosis (SS) of the central nervous system (CNS), which is caused by chronic haemorrhaging into the subarachnoid space with haemosiderin deposition in the superficial portion of the CNS. Patient 1 had fluid collection in the spinal canal, which was reported as the source of the chronic bleeding. Patient 2 was bleeding from thickened dura at the level of the sacral vertebrae. Both of the patients had xanthochromic cerebrospinal fluid. We surgically repaired the sources of bleeding. Subsequently the cerebrospinal fluid (CSF) cleared and their symptoms were not aggravated for about 1 year. We measured several CSF markers of SS before and after surgery. Total tau protein (CSF-t-tau), phosphorylated tau protein (CSF-p-tau), iron (CSF-iron) and ferritin (CSF-ferritin) in the CSF were highly elevated at diagnosis. After surgery, the levels of CSF-t-tau and CSF-p-tau were markedly reduced while CSF-iron and CSF-ferritin had not decreased. It is suggested that CSF-t-tau and CSF-p-tau reflected the neural damage in SS and were useful to evaluate the effectiveness of SS therapies.

Superficial siderosis.

BACKGROUND: Superficial siderosis (SS) of the CNS is caused by repeated slow hemorrhage into the subarachnoid space with resultant hemosiderin deposition in the subpial layers of the brain and spinal cord. Despite extensive investigations, the cause of bleeding is frequently undetermined. OBJECTIVES: To review the clinical and imaging features of 30 consecutive patients with SS and provide insights into the underlying causes of subarachnoid bleeding in this disabling disorder. METHODS: The authors reviewed the medical records of 30 consecutive patients with clinical and MRI evidence of SS. RESULTS: The commonest neurologic manifestations included gait ataxia and hearing impairment. A clinical history of subarachnoid hemorrhage was relatively rare. Possible predisposing conditions were identified on history in 22 patients, the commonest being a prior trauma (15 patients). In addition to the characteristic MRI findings of SS, 18 patients had abnormalities on MRI possibly related to chronic bleeding. The most common of these was the presence of a fluid-filled collection in the spinal canal seen in 14 patients. CONCLUSIONS: A history of prior subarachnoid hemorrhage is often absent in patients with superficial siderosis (SS). A past history of trauma is common. Prior intradural surgery may be an additional risk factor. Xanthochromia or the presence of red blood cells in the CSF is a common finding. Only rarely does angiography demonstrate the bleeding source. The presence of a fluid-filled collection in the spinal canal is a common finding on MRI and is likely related to the SS. With longitudinally extensive cavities, a dynamic CT myelogram may help localize the defect and direct the site of laminectomy. Surgical repair of a dural defect, if present, should be considered. Surgical correction of bleeding should be documented by CSF examination months after surgery. Friable vessels in the dural defect are a possible source of the chronic bleeding.

[Superficial siderosis of the CNS. Case report and literature review]. / Superfizielle Siderose des ZNS. Fallbericht und Literaturübersicht.

Superficial siderosis of the central nervous system is caused by destructive deposition of haemosiderin in the leptomeninges and subpial layers of the brain and spinal cord. This deposition is the result of continuous or recurrent, often clinically silent, haemorrhage in the subarachnoid space, eventually without an evident bleeding source. Cerebellar ataxia, progressive bilateral sensorineural hearing loss, pyramidal tract signs, and dementia are the major clinical findings. The diagnosis is supported in vivo by the characteristic symptom constellation,xanthochromic cerebrospinal fluid,and typical MRI findings which show on the surface of the brainstem, cerebellum, cortex, and spinal cord. Early recognition of this rare entity may be of relevance for the further course and prognosis.

A cycle of cerebrospinal fluid: supporting evidence and theoretical considerations.

An entrenched theory of cerebrospinal fluid (CSF) absorption by the arachnoid villi fails to explain observations regarding the movement of substances in the fluid. Experiments that demonstrated the arachnoid villi as the site of absorption were based on non-physiologic methods. CSF does not flow through the arachnoid villi, because villi require bulk flow and bulk flow of CSF does not exist. CSF is transported through the choroid fissure and recycled through the tela choroidae by the choroid plexus, with reentry into the ventricular system. Observed failures of the effete arachnoid villus theory can be readily explained by the cycling theory. A complete cycle of CSF is suggested to pace the 90 to 100-minute ultradian rhythms found in human physiology.

Elevated CSF lactoferrin in superficial siderosis of the central nervous system.

This study sought to identify abnormalities in the levels of iron transport proteins in patients with superficial siderosis of the central nervous system. We compared patients with superficial siderosis (n = 7) with patients suffering from various other neurological disorders (n = 176, total). CSF and serum levels of lactoferrin, and CSF levels of transferrin were measured by enzyme-linked immunosorbent assay. Serum transferrin was measured by nephelometry. Lactoferrin, but not transferrin, levels in the CSF were significantly elevated in superficial siderosis. Unexpectedly, CSF transferrin was decreased in multiple sclerosis patients. Enhanced CSF lactoferrin may reflect an increased iron transport requirement in the central nervous system in superficial siderosis and might be a useful measure for monitoring response to therapy.

[Superficial siderosis of the central nervous system]. / Hémosidérose du système nerveux central.

We report five cases of superficial siderosis of the central nervous system. All patients developed progressive deafness and cerebellar ataxia associated with pyramidal tract signs or mental deterioration. The cerebrospinal fluid examinations usually revealed an elevated protein level, without other abnormalities. Magnetic resonance imaging typically showed a hypointense rim around the cerebral and cerebellar hemispheres, the brainstem and the spinal cord on T2-weighted images. A definite source of bleeding was only found in two patients. The literature on superficial siderosis is reviewed. The etiologies and the pathogenesis are discussed.

Spinal meningeal melanocytoma presenting with superficial siderosis of the central nervous system. Case report and review of the literature.

Meningeal melanocytoma is a benign melanocytic tumor that originates most frequently from the melanocytes in the posterior fossa or along the spinal cord. This tumor generally occurs as an extraaxial mass that compresses adjacent neural structures to produce various neurological signs. The authors describe an unusual case in which a patient with a meningeal melanocytoma located at the thoracic spinal cord presented with superficial siderosis of the central nervous system (CNS). Extensive neuroradiological studies identified the presence of a spinal cord tumor, and postsurgical histological examination revealed the meningeal melanocytoma as a bleeding source. After surgery, lumbar puncture demonstrated normalization of the patient's cerebrospinal fluid; however, no neurological improvement occurred. The neurological deficits seem irreversible. Meningeal melanocytoma is biologically benign and can be cured by complete surgical resection; therefore, this tumor should be included in the differential diagnosis of pigmented lesions of the CNS. The authors reviewed 14 cases of well-documented meningeal melanocytoma in the literature and discuss the clinical, radiological, and pathological features of the present case to emphasize the importance of early diagnosis and identification of the source of bleeding in patients with superficial siderosis.

Superficial siderosis of the brain: roles for cerebrospinal fluid circulation, iron and the hydroxyl radical.

Superficial siderosis is associated with chronic blood loss into the cerebrospinal fluid. The pattern of hemosiderin deposition and clinical signs in superficial siderosis suggest that cerebrospinal fluid is recirculated into the ventricular system. Patterns of deposition of corpora amylacea and findings in normopressure communicating hydrocephalus also support the recirculation theory. 'Free' iron with excess production of hydroxyl radicals is the probable mechanism of tissue damage. The arachnoid villus-superior saggital sinus theory of cerebrospinal fluid circulation should be abandoned.

[Two cases of superficial siderosis of the central nervous system. Findings of the cerebrospinal fluid, magnetic resonance imaging and positron emission tomography].

Two cases (case 1, a 45-year-old man; case 2, a 68-year-old man) of superficial siderosis of the central nervous system are presented. Main neurological symptoms were anosmia, sensorineural deafness, dysarthria, ataxia, and pyramidal tract signs. Lumbar puncture revealed bloody cerebrospinal fluid (CSF) in both cases. In case 1, the CSF became watery clear after administration of hemostatic medicines. T2-weighted magnetic resonance images showed cerebellar atrophy and marginal hypointensity of the brainstem, cerebellum, and the entire spinal cord. T2-weighted images of the cranial nerves showed hypointensity of the VIII nerves which were clinically impaired as compared with normointensity of the VII nerves which presented no clinical symptom. These findings may reflect difference in the degree of hemosiderin depostion between the VII and VIII nerves. While case 1 had a borderline score of WAIS-R (IQ79), case 2 showed overt dementia (performance IQ65). Positron emission tomography showed that cerebral blood flow and cerebral oxygen metabolism were reduced in the basal temporal lobes in both cases.

The pathogenesis of superficial siderosis of the central nervous system.

In advanced cases of superficial siderosis of the human central nervous system, the clinical triad of hearing loss, cerebellar ataxia, and myelopathy permits the diagnosis at the bedside, and magnetic resonance imaging readily confirms the hemosiderin deposits in brainstem, cerebellum, and spinal cord. To study the pathogenesis of this condition and explain the selective vulnerability of the cerebellum, experimental siderosis was induced in rabbits by the repeated intracisternal injection of autologous red blood cells. The earliest cellular response in the cerebellar molecular layer was hyperplasia and hypertrophy of microglia as displayed by immunocytochemistry for ferritin. Microglia also contained iron, but ferritin biosynthesis appeared to proceed without commensurate iron accumulation. This early apoferritin response probably occurred due to the presence of heme, rather than iron, in the cerebrospinal fluid and subpial tissue. Ferritin biosynthesis is accelerated when the ferritin repressor protein is dissociated from ferritin messenger ribonucleic acid. A specific antiserum localized ferritin repressor protein predominantly to astrocytes including Bergmann glia. It is proposed that abundance and proximity of ferritin repressor protein--immunoreactive Bergmann glia and ferritin-containing microglia in the cerebellar molecular layer permit prompt cellular interaction in the conversion of heme to ferritin and ultimately hemosiderin.

Superficial siderosis of the central nervous system: report of three cases and review of the literature.

We present 3 cases and a review of the literature to demonstrate the current state of clinical diagnosis and therapy of superficial siderosis of the central nervous system. Typical symptoms were progressive cerebellar ataxia, spasticity and hearing loss. Repeated subarachnoid hemorrhage was indicated by persistent xanthochromia of the cerebrospinal fluid and confirmed by the presence of erythrophages, siderophages and iron-containing pigments. Deposition of free iron and hemosiderin in pial and subpial structures leads to intoxication of the central nervous system and represents the pathophysiological mechanism of superficial siderosis. Hypointensity of the marginal zones of the central nervous system on T2 weighted MR images indicates an iron-induced susceptibility effect and seems pathognomonic for superficial siderosis. In 39 of the 43 previously described cases superficial siderosis was verified by biopsy or autopsy. Today magnetic resonance imaging enables diagnosis at an early stage of the disease. Therapeutic management requires the elimination of any potential source of bleeding. In patients with unknown etiology no proofed therapy is yet available.