Central Nervous System Siderosis Associated with Multiple Cerebral Aneurysms: Literature Review and Description of an Additional Case.

BACKGROUND: Superficial siderosis (SS) of the central nervous system is a rare disease characterized by deposition of hemosiderin along the leptomeninges due to chronic or recurrent bleeding into the subarachnoid space. The association of unruptured intracranial aneurysm (IA) and cortical SS is quite rare. METHODS: A systematic literature review to assess possible commonalities and/or differences of previous reported cases was undertaken. We report an additional case from our institution. RESULTS: A 40-year-old woman presented with a history of generalized seizures over the past year. There was no clinical history suggestive of aneurysm rupture. Magnetic resonance imaging revealed 2 aneurysms of the right middle cerebral artery (MCA) bifurcation associated with hemosiderin deposition along the right sylvian fissure and a third aneurysm of the left MCA bifurcation. Magnetic resonance imaging showed wall enhancing thickening of the larger right MCA aneurysm. The patient underwent surgical clipping of all 3 MCA aneurysms in a staged procedure. Histological examination revealed hemosiderin deposits within the aneurysm wall and surrounding gliosis. CONCLUSIONS: Our literature review found 24 reported cases of unruptured IA associated with cortical SS. The possible source for leakages could be neovessels visible in IA walls. The case reported illustrates an uncommon presentation of recurrent bleeding from an IA as a source of SS. The presence of an apparently unruptured IA surrounded by cortical SS on imaging studies is of high relevance as this should be considered a sign of aneurysm wall instability and should indicate prompt treatment.

Superficial siderosis of the central nervous system：A literature analysis and case report / 中风与神经疾病杂志

@#Objective To investigate the etiology，clinical manifestations，imaging features，and treatment of superficial siderosis of the central nervous system （SSCNS）. Methods A patient confirmed with SSCNS was reported.Sixty-one patients confirmed with SSCNS were found through a search of China National Knowledge Infrastructure and Wanfang Data and were analyzed in categories for the epidemiology， etiology， clinical manifestations， and laboratory test results. Results Among the 61 patients with SSCNS reported in the literature， ataxia was the most common clinical symptom （49 cases， 80%）， followed by hearing loss （43 cases，70%） and pyramidal signs（30 cases， 49%）.A probable cause was found in 25 （39%） of these cases. Conclusion SSCNS can last for several years or even decades， with hearing loss， ataxia， and pyramidal signs as its main clinical symptoms.Magnetic resonance imaging is the most valuable basis for diagnosis， and susceptibility-weighted imaging is more sensitive in the diagnosis of microhemorrhage.

Quantitative clinical and radiological recovery in post-operative patients with superficial siderosis by an iron chelator.

BACKGROUND: Superficial siderosis is a rare neurodegenerative disease caused by hemosiderin deposition on the brain surface. Although the efficacy of the iron chelator-deferiprone-in superficial siderosis has recently been documented, a comparative study of patients who underwent surgical ablation of their bleeding source and subsequently received treatment with or without deferiprone has not yet been conducted. METHODS: Fifteen postoperative patients with superficial siderosis were recruited, and seven patients were administered deferiprone (combination therapy group). Quantitative changes in the hypointense signals on T2*-weighted magnetic resonance images were acquired; additionally, cerebellar ataxia was assessed (International Cooperative Ataxia Rating Scale score and Scale for the Assessment and Rating of Ataxia). Audiometry was performed and the results were compared with those of patients who did not receive deferiprone (surgical treatment group; controls). RESULTS: Significant improvements in signal contrast ratios were noted in the lateral orbitofrontal gyrus, superior temporal lobe, insular lobe, brainstem, lingual gyrus, and cerebellar lobe in the combination therapy group. The scores of patients in the combination therapy group on the cerebellar ataxia scales significantly improved. The degree of signal improvement in the cerebellar lobe correlated with the improvement of cerebellar ataxia scores. Early deferiprone administration after disease onset and long-term administration were correlated with greater signal improvements on magnetic resonance imaging. No adverse effects were observed in the clinical or laboratory parameters. CONCLUSIONS: Deferiprone administration significantly improved radiological and clinical outcomes in patients with postoperative superficial siderosis. Earlier and longer courses of deferiprone could result in better patient prognosis.

Predictive factors and prognosis of post-stroke seizures / 中华行为医学与脑科学杂志

Objective:To assess the predictive factors and prognosis of post-stroke seizures.Methods:A total of 315 inpatients with acute anterior circulation cerebral infarction from January 2018 to December 2018 were retrospectively collected, including 95 patients with PSS as observation group and 220 patients without PSS as control group.Clinical characteristics of the patients were recorded, including gender, age, lesion specificity, imaging features, past history, and the time and type of seizures.The Alberta stroke program early CT score (ASPECTS) was used to assess the extent of infarction, the national institutes of health stroke scale (NIHSS) and the modified rankin scale (MRS) were used to assess the severity and prognosis of cerebral infarction.The hemorrhage transformation of cerebral infarction was graded according to the European cooperative acute stroke study Ⅲ(ECASS Ⅲ) classification system.SPSS 21.0 software was used for data analysis.Chi-square test was used for categorical variables and t-test or non-parametric test was used for continuous variables. Results:The observation group had lower ASPECTS scores compared with the control group (5(4, 7), 7 (5, 8)), the presence of atrial fibrillation, hemorrhage transformation, laminar necrosis(LN) and hemosiderin deposition (31.6%, 45.3%, 24.2%, 26.3%) were higher than those of control group (20.9%, 28.2%, 9.1%, 16.4%), and the differences were statistically significant (all P<0.05). In multivariate analysis, ASPECTS score ( OR=0.658, 95% CI=0.556-0.778, P<0.001), hemorrhage transformation ( OR=2.307, 95% CI=1.311-4.059, P=0.004), LN ( OR=2.530, 95% CI=1.250-5.123, P=0.010) and hemosiderin deposition ( OR=2.308, 95% CI=1.201-4.436, P=0.012) were the influencing factors of PSS.Partial secondary generalized seizures was the most common type of seizures, and in this group it accounted for 42.1% (40/95), simple partial seizures and complex partial seizures accounted for 12.6% (12/95)respectively, and generalized seizures accounted for 32.6% (31/95). The mean follow-up time of the two groups was 24.1 months and 24.6 months, respectively.The scores of MRS at the last follow-up and discharge (3(2, 4), 2(1, 4)) of the observation group were better than those of the control group (2(1, 3), 1(1, 3)), and the differences were statistically significant(both P<0.05). Conclusions:PSS after cerebral infarction can affect the prognosis of patients, and the large infarction scope, hemorrhage transformation, LN and hemosiderin deposition are the high risk factors of PSS.

Hemosiderin deposition evaluation in hemophilic ankle joints: association between US finding and gradient-recalled echo MR imaging sequence.

BACKGROUND: Repeated bleeding in hemophilic arthropathy (HA) may result in severe degenerative changes and joint destruction. The gradient-recalled echo (GRE) sequence MR is proved to be the best method to detect hemosiderin deposition. However, MR is not widely available in developing countries, including Indonesia. Some studies have proposed ultrasonography (US) as an alternative tool in evaluating hemophilic joint. However, there is still some disagreement on the ability of US to detect hemosiderin deposition. OBJECTIVE: To evaluate the association between US and GRE-sequence MR imaging in detecting hemosiderin deposition in hemophilic ankle joint. MATERIAL AND METHODS: A total of 102 sites from 17 ankle joints of 11 boys with severe hemophilia A underwent US examination using a high-frequency linear array transducer. GRE-sequence MR examination was performed in sagittal view consistent with the sites scanned by US. Both examinations were performed on the same day, but MR interpretation was performed blindly at different times. The association between US and GRE-sequences in detecting hemosiderin deposition was analyzed using McNemar's test. RESULTS: Statistical analysis showed a significant association (p value < 0.001) between US and GRE MR in detecting hemosiderin deposition, but the association is weak (R = 0.26). Sensitivity and specificity of US for detecting hemosiderin deposition were 46.84% (95%CI: 35.51-58.40) and 95.65% (95%CI: 78.05-99.89), respectively, with positive predictive value 97.37% (95%CI: 84.29-99.61), negative predictive value 34.38% (95%CI: 29.50-39.60) and accuracy 57.84% (95%CI: 47.66-67.56). CONCLUSION: There was a weak association between US and GRE-sequences in detecting hemosiderin deposition of hemophilic ankle joint. â€‹â€‹.

Hemodynamic features of an intracranial aneurysm rupture predicted by perianeurysmal edema: A case report.

BACKGROUND: Perianeurysmal edema (PAE) has been suggested as an indicator of potential aneurysm rupture; however, the hemodynamic features of these aneurysms are still unknown. A computational fluid dynamic (CFD) analysis was performed to evaluate the hemodynamic features of a very rare case of a ruptured middle cerebral artery (MCA) aneurysm with PAE. CASE DESCRIPTION: A 65-year-old woman presented with disturbed consciousness. A subarachnoid hemorrhage due to an azygos anterior cerebral artery (ACA) aneurysm rupture was suspected. An unruptured MCA aneurysm with PAE was identified in the left temporal lobe. Although the ACA aneurysm was clipped to prevent re-bleeding, the MCA aneurysm subsequently ruptured 6 days later. Clipping of the MCA aneurysm was performed, and hemosiderin deposits suggestive of sentinel bleeding were found on the surface of the aneurysm dome. CFD analysis revealed unstable hemodynamic stress at the expanded bleb area after rupture, localized to the rupture site. Moreover, this analysis revealed flow impingement with pressure elevation and low wall shear stress, which indicated increased inflammation and aneurysm wall thinning that likely led to rupture. CONCLUSION: Hemosiderin deposits at the aneurysm wall and PAE indicates leakage from a cerebral aneurysm. Hemodynamic stress at the aneurysm may promote an inflammatory response and lead to wall weakening accompanied by PAE. Based on our findings, we recommend that surgical intervention should be considered as the first line of treatment for such aneurysms to prevent rupture.

Hemosiderin deposition in lymph nodes of patients with plasma cell-type Castleman disease.

Plasma cell-type Castleman disease (PCD) is a rare idiopathic atypical lymphoproliferative disorder. It is difficult to differentiate between PCD and IgG4-related disease (IgG4-RD) based on histology alone. As PCD often presents with abundant hemosiderin deposition, lymph node lesions obtained from 22 PCD patients and 12 IgG4-RD patients were analyzed using Prussian blue staining to clarify whether hemosiderin deposition is effective in distinguishing between these two diseases. The analysis disclosed that hemosiderin was more densely deposited in PCD than in IgG4-RD. The median number of Prussian blue-positive cells ± standard deviation (SD) in PCD and IgG4-RD cases was 13 ± 36 cells/3HPFs and 4 ± 8 cells/3HPFs (P = 0.034), respectively. In addition, we analyzed the relationship between hemosiderin deposition and levels of serum interleukin (IL)-6, serum C-reactive protein (CRP), and anemia-related biomarkers. We found that hemosiderin deposition was significantly correlated with the level of serum CRP (P = 0.045); however, no significant correlation was observed between hemosiderin deposition and serum IL-6 levels (P = 0.204). A non-significant positive correlation was observed between hemosiderin deposition and serum hemoglobin levels (P=0.09). Furthermore, no significant correlation was observed between hemosiderin deposition and serum iron levels (P = 0.799). In conclusion, hemosiderin deposition characteristically observed in PCD may be related to the inflammatory aggressiveness of the disease and could be used for its differential diagnosis.

Outcome and predictive factors in post-stroke seizures: A retrospective case-control study.

PURPOSE: To evaluate clinical, radiographic, and electrophysiological features in the development and prognosis of ischemic post-stroke seizures (PSS). METHOD: A retrospective study of 1119 patient records was performed between January 2006 and December 2016. After selection, 42 patients with seizures due to ischemic stroke were matched to a control group of 60 patients where seizures were absent. Stroke size and severity were analyzed using ASPECTS and NIHSS, respectively. Hemorrhagic transformation graded by ECASS III classification. Outcomes were assessed using the modified Rankin Scale. Fisher's exact test assessed categorical variables, and Mann-Whitney tested continuous variables. RESULTS: Forty-two patients experienced PSS (22 females; median age 72.5 years) and were matched with 60 control subjects that had ischemic stroke without seizures. Focal seizures were present in 42.9% (18/42), and focal to bilateral convulsions in 57.1% (24/42). Stroke localization and severity did not differ (p = 0.6 and 0.21, respectively). Stroke size in anterior circulation was larger in PSS patients (median ASPECTS 6 vs 8 [p = 0.01]). Posterior circulation stroke size was similar in both groups. The presence of hemorrhage was the primary risk factor for PSS (61.9%) compared to controls (36.7%), p = 0.01. The presence of laminar necrosis (LN) (47.6% vs 21.6%, p = 0.005) and hemosiderin deposition (38.1% vs 18.3%, p = 0.02) were most predictive. PSS patients demonstrated worse outcomes than the controls (median mRS 3 vs 2, [p=<0.001]) with a median follow up of 14.8 and 20.7 months, respectively. CONCLUSIONS: The size of anterior infarction, presence of blood products within the infarct bed, and especially LN predicted PSS.

Superficial siderosis: Chronic sequelae following brain hemorrhage.

Superficial siderosis is a rare disease of the central nervous system. It is caused by hemosiderin deposition usually following subarachnoid hemorrhage. We report a 67-year-old man with history of motor vehicle accident in 1974 who presents with tremors, worsening ataxia, and impaired auditory, olfactory, and gustatory sensation. The patient was evaluated with magnetic resonance imaging of the brain that showed areas of superficial low T2 signal throughout the posterior fossa, ventricles, sulci, and cisterns, most conspicuous on the gradient-recalled echo T2* susceptibility-weighted sequence. These findings are compatible with old blood products (hemosiderin) and the diagnosis of superficial siderosis.

Microbleeds and cavernomas after radiotherapy for paediatric primary brain tumours.

BACKGROUND: With the expected growth and aging of the population of primary central nervous system tumours (PCNST) survivors, attention to the radiation-induced late brain injury is fundamental. Late focal hemosiderin deposition (FHD) lesions, namely microbleeds and cavernomas, are among the presumable late cerebrovascular complications associated with radiotherapy for PCNST. OBJECTIVE: To explore association between PCNST radiotherapy and the occurrence FHD lesions and to address the correlation between the topographic location of these microvascular lesions with the focal radiotherapy location. METHODS: Retrospective cohort study of 190 paediatric patients being followed for PCNST in a single referral oncological centre. The frequency of FHD lesions was compared between paediatric PCNST treated (n=132) and not treated (n=58) with brain radiation. Microbleed Anatomical Rating Scale (MARS) was used for systematic identification of these cerebrovascular lesions and to address the consistency between the topographic location of each lesion and the location of the focal radiotherapy area. Univariate analysis to address the role of variables such as tumour histology, location, gender and age of children at the beginning of radiotherapy, duration of follow-up and chemotherapy was performed. RESULTS: FHD lesions (microbleeds and cavernomas) occurred exclusively and in a high percentage (41.6%) in PCNST survivors treated with brain radiation. Younger age at the diagnosis (p=0.031), duration of follow-up (p=0.010) and embryonal histology (p=0.003) positively correlated with the occurrence FHD lesions. FHD lesions were topographically concordant with the brain focal irradiation area in 3/19 (15.8%) patients from the focal RT subgroup and in 22/111 (19.8%) patients from the WBRT plus focal RT subgroup. CONCLUSION: Our study, which is one of the largest to date on the topic, shows that FHD lesions are a common complication after radiotherapy for childhood PCNST. The young brain is probably more susceptible to radiation-induced late cerebrovascular injury. Diffuse small vessel disease and ceiling effect may account for the low topographic concordance we found. The clinical implications of FHD lesions in this specific population are yet to be clarified.

The significance of hemosiderin deposition in the lungs and organs of the mononucleated macrophage resorption system in infants and children.

Hemosiderin deposition is not often recognized on routine examination with hematoxylin and eosin staining; however, iron stains may be helpful in the evaluation of hemosiderin deposition in infant autopsies. This report describes the data obtained from autopsy of 86 infants and children whose deaths were investigated at the Forensic Medicine Council Bursa Morgue Department from January 2000 to January 2003. A histochemical technique was used to identify hemosiderin in lung, liver and spleen specimens, which was correlated with other descriptive variables such as the reported cause of death, postmortem interval, trauma history, gender, and age. There was a weakly positive but significant correlation between lung and liver hemosiderin scores (Spearman's rank correlation coefficient, rho=0.348, p=0.001); i.e., given an increase in lung hemosiderin scores, an increase in liver hemosiderin scores was also observed. Similarly, a marked positive correlation between spleen and liver hemosiderin scores (Spearman's rank correlation coefficient, rho=0.335, p=0.002) was observed. The probability of spleen hemosiderin-positive cases belonging to the age group under 6 months was found to be 4.3 times greater than those who were hemosiderin-negative (95% confidence interval, 1.6-11.8). After the major differential diagnoses were ruled out, this study demonstrated, that depending on the statistically assessed morphometric grounds, the presence of hemosiderin deposits in the liver and spleen were significantly higher in the age group under 6 months.

The Significance of Hemosiderin Deposition in the Lungs and Organs of the Mononucleated Macrophage Resorption System in Infants and Children

Hemosiderin deposition is not often recognized on routine examination with hematoxylin and eosin staining; however, iron stains may be helpful in the evaluation of hemosiderin deposition in infant autopsies. This report describes the data obtained from autopsy of 86 infants and children whose deaths were investigated at the Forensic Medicine Council Bursa Morgue Department from January 2000 to January 2003. A histochemical technique was used to identify hemosiderin in lung, liver and spleen specimens, which was correlated with other descriptive variables such as the reported cause of death, postmortem interval, trauma history, gender, and age. There was a weakly positive but significant correlation between lung and liver hemosiderin scores (Spearman's rank correlation coefficient, rho=0.348, p=0.001); i.e., given an increase in lung hemosiderin scores, an increase in liver hemosiderin scores was also observed. Similarly, a marked positive correlation between spleen and liver hemosiderin scores (Spearman's rank correlation coefficient, rho=0.335, p=0.002) was observed. The probability of spleen hemosiderin-positive cases belonging to the age group under 6 months was found to be 4.3 times greater than those who were hemosiderin-negative (95% confidence interval, 1.6-11.8). After the major differential diagnoses were ruled out, this study demonstrated, that depending on the statistically assessed morphometric grounds, the presence of hemosiderin deposits in the liver and spleen were significantly higher in the age group under 6 months.