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

Abstract

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 one 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.-2 -CSF tau protein in superficial siderosis

Elevation of 8‐hydroxy‐2′‐deoxyguanosine in the cerebrospinal fluid of three patients with superficial siderosis

“…Although a decrease of CSF t‐tau was observed after surgical repair of bleeding origin in our cases, as reported in a previous study, 8‐OHdG levels did not decrease and symptoms continued to progress after surgical treatment . As an interpretation, as surgical treatment stopped bleeding, but did not readily remove iron deposits in the central nervous system, continuing oxidative stress would produce 8‐OHdG and might modestly damage the central nervous system as long as iron deposits persist.…”

Superficial siderosis associated with abundant and -synuclein accumulation

“…An increased level of τ protein in CSF is an important biomarker for the clinical diagnosis of Alzheimer’s disease because it suggests an abnormal accumulation of τ protein in the brain parenchyma 29. Although it was impossible to evaluate the τ levels in CSF for this patient, the pathologic findings of this and other studies27 28 strongly suggest that τ accumulation in neurons and glia may be a common pathologic alteration of superficial siderosis.…”

“…In addition to some NFTs in the hippocampus and parahippocampus, we found abundant glial τ accumulation in the cerebellum and in nerve roots with severe hemosiderin deposits. Importantly, two papers have mentioned increased levels of τ and phosphorylated τ protein in the CSF of individuals with superficial siderosis 27 28. An increased level of τ protein in CSF is an important biomarker for the clinical diagnosis of Alzheimer’s disease because it suggests an abnormal accumulation of τ protein in the brain parenchyma 29.…”

CSF in Alzheimer's Disease

“…In the meantime, we should make use of the AD specificity for P-tau elevations. There are at present only three conditions in addition to AD in which elevated CSF P-tau has been reported: (i) in term and preterm newborns, possibly reflecting physiological tau phosphorylation in brain development [87], (ii) in herpes encephalitis [88], and (iii) in superficial CNS siderosis [89,90]. Clearly, these conditions are no important differential diagnoses to AD, but they may shed light on mechanisms behind CSF P-tau increase (as may the data on tau phosphorylation in hibernating squirrels [91] and hamsters [92]).…”