Cochlea implantation in patients with superficial hemosiderosis.

INTRODUCTION: Superficial hemosiderosis is a sub-form of hemosiderosis in which the deposits of hemosiderin in the central nervous system damage the nerve cells. This form of siderosis is caused by chronic cerebral hemorrhages, especially subarachnoid hemorrhages. The diversity of symptoms depends on the respective damage to the brain, but in most of the cases it shows up as incipient unilateral or bilateral hearing loss, ataxia and signs of pyramidal tracts. We are investigating the question of whether cochlear implantation is a treatment option for patients with superficial hemosiderosis and which strategy of diagnostic procedure has to be ruled out preoperatively. MATERIALS AND METHODS: In a tertiary hospital between 2009 and 2018, we examined (N = 5) patients with radiologically confirmed central hemosiderosis who suffered from profound hearing loss to deafness were treated with a cochlear implant (CI). We compared pre- and postoperative speech comprehension (Freiburg speech intelligibility test for monosyllables and HSM sentence test). RESULTS: Speech understanding improved on average by 20% (monosyllabic test in the Freiburg speech intelligibility test) and by 40% in noise (HSM sentence test) compared to preoperative speech understanding with optimized hearing aids. DISCUSSION: The results show that patients with superficial siderosis benefit from CI with better speech understanding. The results are below the average for all postlingual deaf CI patients. Superficial siderosis causes neural damages, which explains the reduced speech understanding based on central hearing loss. It is important to correctly weigh the patient's expectations preoperatively and to include neurologists within the therapy procedure.

Detection and monitoring of subclinical ocular siderosis using multifocal electroretinogram.

BACKGROUND: Although full-field electroretinogram (ffERG) is the gold standard test to detect physiological dysfunction in siderosis, it measures overall retinal function. This study aims to determine if multifocal electroretinogram (mfERG) can detect subclinical siderosis in eyes with an iron intraocular foreign body (IOFB). METHODS: Twenty eyes of 20 patients with retained iron IOFB, clear ocular media and good visual acuity (≥20/120) were enroled in this prospective case-control study. The fellow eyes served as control. These were evaluated with ffERG and mfERG at baseline. Serial mfERG was done till six months after pars plana vitrectomy with IOFB removal. Primary outcomes measures were amplitude and peak time of P1 and N1 wave of mfERG. RESULTS: The median age was 25 years (range 18-55). Most patients (n = 14/20) presented within a month of trauma. Baseline ffERG showed no difference in either 'a' or 'b' wave amplitude or peak time between cases and controls. However, on mfERG, there was a significant decrease in P1 and N1 wave amplitude and delay in P1 wave peak time in <2° retinal ring in cases as compared to controls (p = 0.001, 0.001 and 0.02 respectively) despite variability in results. At 6 months, P1 amplitude showed significant improvement from baseline in cases (p = 0.010). However, P1 peak time did not show significant recovery (p = 0.65). CONCLUSIONS: mfERG may reveal subclinical electrophysiological retinal dysfunction in eyes with iron IOFB in cases with normal ffERG. P1 peak time may serve as an electrophysiological marker for past retinal damage.

Creation and validation of a simulator for corneal rust ring removal.

OBJECTIVE: To create and validate a simulation model for corneal rust ring removal. METHODS: Rust rings were created on cadaveric eyes with the use of small particles of metal. The eyes were mounted on suction plates at slit lamps and the trainees practiced rust ring removal. An inexperienced cohort of medical students and first year ophthalmology residents (n=11), and an experienced cohort of senior residents and faculty (n=11) removed the rust rings from the eyes with the use of a burr. Rust ring removal was evaluated based on removal time, percentage of rust removed and incidence of corneal perforation. A survey was administered to participants to determine face validity. RESULTS: Time for rust ring removal was longer in the inexperienced group at 187±93 seconds (range of 66-408 seconds), compared to the experienced group at 117±54 seconds (range of 55-240 seconds) (p=0.046). Removal speed was similar between groups, at 4847±4355 pixels/minute and 7206±5181 pixels/minute in the inexperienced and experienced groups, respectively (p=0.26). Removal percentage values were similar between groups, at 61±15% and 69±18% (p=0.38). There were no corneal perforations. 100% (22/22) of survey respondents believed the simulator would be a valuable practice tool, and 89% (17/19) felt the simulation was a valid representation of the clinical correlate. CONCLUSION: The corneal rust ring simulator presented here is a valid training tool that could be used by early trainees to gain greater comfort level before attempting rust ring removal on a live patient.

Post-mortem study of the association between cardiac iron and fibrosis in transfusion dependent anaemia.

BACKGROUND: Heart failure related to cardiac siderosis remains a major cause of death in transfusion dependent anaemias. Replacement fibrosis has been reported as causative of heart failure in siderotic cardiomyopathy in historical reports, but these findings do not accord with the reversible nature of siderotic heart failure achievable with intensive iron chelation. METHODS: Ten whole human hearts (9 beta-thalassemia major, 1 sideroblastic anaemia) were examined for iron loading and fibrosis (replacement and interstitial). Five had died from heart failure, 4 had cardiac transplantation for heart failure, and 1 had no heart failure (death from a stroke). Heart samples iron content was measured using atomic emission spectroscopy. Interstitial fibrosis was quantified by computer using picrosirius red (PSR) staining and expressed as collagen volume fraction (CVF) with normal value for left ventricle <3%. RESULTS: The 9 hearts affected by heart failure had severe iron loading with very low T2* of 5.0 ± 2.0 ms (iron concentration 8.5 ± 7.0 mg/g dw) and diffuse granular myocardial iron deposition. In none of the 10 hearts was significant macroscopic replacement fibrosis present. In only 2 hearts was interstitial fibrosis present, but with low CVF: in one patient with no cardiac siderosis (death by stroke, CVF 5.9%) and in a heart failure patient (CVF 2%). In the remaining 8 patients, no interstitial fibrosis was seen despite all having severe cardiac siderosis and heart failure (CVF 1.86% ±0.87%). CONCLUSION: Replacement cardiac fibrosis was not seen in the 9 post-mortem hearts from patients with severe cardiac siderosis and heart failure leading to death or transplantation, which contrasts markedly to historical reports. Minor interstitial fibrosis was also unusual and very limited in extent. These findings accord with the potential for reversibility of heart failure seen in iron overload cardiomyopathy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00520559.

Superficial siderosis of the central nervous system associated with intraspinal hemorrhage from ventral thoracic epidural veins and a ventral spinal CSF leak: case report.

In most patients with superficial siderosis of the CNS, the exact source of bleeding remains unknown because of a lack of objective surgical data. The authors herein describe the case of a 58-year-old man with superficial siderosis of the CNS. The patient also had spinal CSF leakage due to a spinal dural defect. Repair surgery for the dural defect was performed using posterior laminoplasty with a transdural approach without spinal fixation. During repair surgery, the bleeding source was found to be the epidural vein around the defect. The intraoperative and histological results of the present case suggest that epidural veins exposed to CSF represent a chronic bleeding source in patients with superficial siderosis of the CNS complicated by CSF leakage. Dural repair surgery may result in discontinuation of the CSF leaks, resolution of the epidural CSF collection, and cessation of chronic epidural bleeding.

Cytologic and Histologic Features of Pleomorphic Undifferentiated Sarcoma Arising in a Hybrid Hemosiderotic Fibrolipomatous Tumor and Pleomorphic Hyalinizing Angiectatic Tumor: Report of an Unusual Case with a Literature Review.

BACKGROUND: Pleomorphic hyalinizing angiectatic tumor (PHAT) and hemosiderotic fibrolipomatous tumor (HFLT) are low-grade neoplasms that share clinicopathologic features and recurring translocation t(1;10)(p22;q24) involving the TGFBR3 and MGEA5 genes. Coexistence of these tumors with a high-grade sarcoma is exceedingly rare and the cytologic features have not been widely described in the literature. CASE: A 55-year-old female presented with a soft tissue tumor on the dorsum of the foot. Cytologic smears and corresponding core biopsies were composed of a population of markedly pleomorphic spindle cells seen singly and in loose clusters within a myxofibrous matrix and infiltrating fat, with coarse chromatin, prominent nucleoli, irregular nuclear contours and delicate to vacuolated cytoplasm. Intracytoplasmic hemosiderin granules and rare intranuclear cytoplasmic pseudoinclusions were identified. The histologic features of the excisional biopsy mirrored those of the cytologic preparations, but also demonstrated cellular foci of higher-grade sarcoma composed of markedly pleomorphic tumor cells with large vesicular nuclei and prominent nucleoli, exhibiting a mitotic index of 12 mitotic figures per 10 high-powered fields. CONCLUSION: While HFLT/PHAT generally can be managed by wide local excision, it is important to be aware of their capacity to harbor higher-grade lesions with metastatic potential which may require more radical surgical excision.

Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies.

Seizure outcome after surgical resection of supratentorial cavernous malformations plus hemosiderin rim in patients with short duration of epilepsy.

OBJECTIVE: The objective of this study was to retrospectively review the postoperative seizure outcome in patients with short duration of epilepsy associated with cavernous malformations and analyze the effect of surgical methods on seizure outcome in such population. METHODS: 36 patients with short duration of epilepsy (shorter than 12 months) associated with cavernous malformations in temporal or frontal lobe underwent microsurgical resection. The patients were retrospectively divided into two groups: Group A (21 patients) with complete removal of hemosiderin rim and Group B (15 patients) with partial removal of hemosiderin rim. Clinical follow-up was achieved with telephone correspondence or outpatient assessment. The seizure outcome was based on Engel's classification. RESULTS: After a mean follow-up period of 18 months, 77.8% of the patients (28/36) were classified into Engel class I, including 19 patients (90.5%) in the complete removal of hemosiderin rim group (Group A) and 9 patients (60%) in the partial removal of hemosiderin rim group (Group B). Seizure outcome was significantly better in Group A. There was no mortality and all the postoperative neurological deficits were recovered at the time of follow-up. CONCLUSION: The analysis of the seizure outcome demonstrate patients with short duration of epilepsy associated with cavernous malformations could benefit greatly from complete resection of hemosiderin rim and cavernous malformations.

Dural closure for the treatment of superficial siderosis.

Superficial siderosis (SS) of the CNS is a rare disease caused by repeated hemorrhages in the subarachnoid space. The subsequent deposition of hemosiderin in the brain and spinal cord leads to the progression of neurological deficits. The causes of bleeding include prior intradural surgery, carcinoma, arteriovenous malformation, nerve root avulsion, and dural abnormality. Recently, surgical treatment of SS associated with dural defect has been reported. The authors of the present report describe 2 surgically treated SS cases and review the literature on surgically treated SS. The patients had dural defects with fluid-filled collections in the spinal canal. In both cases, the dural defects were successfully closed, and the fluid collection was resolved postoperatively. In one case, the neurological symptoms did not progress postoperatively. In the other case, the patient had long history of SS, and the clinical manifestations partially deteriorated after surgery, despite the successful dural closure. In previously reported surgically treated cases, the dural defects were closed by sutures, patches, fibrin glue, or muscle/fat grafting. Regardless of the closing method, dural defect closure has been shown to stop CSF leakage and subarachnoid hemorrhaging. Successfully repairing the defect can halt the disease progression in most cases and may improve the symptoms that are associated with CSF hypovolemia. However, the effect of the dural closure may be limited in patients with long histories of SS because of the irreversibility of the neural tissue damage caused by hemosiderin deposition. In patients with SS, it is important to diagnose and repair the dural defect early to minimize the neurological impairments that are associated with dural defects.

Cochlear implantation in patients affected by superficial hemosiderosis of the central nervous system.

The objectives of the study were to: report three more cases of cochlear implantation (CI) in patients affected by superficial hemosiderosis of the central nervous system (SH-CNS); assess whether CI may be a viable option in this disease. The study was conducted in a tertiary referral center. Pre-operative and post-operative clinical notes of three patients with SH-CNS were reviewed. Two out of three cases showed very good results with CI in sentence perception in noise over 90%. For the other case, hearing performance was very low. He showed only disyllabic word identification abilities in a closed set (40%). Cochlear implantation may be a viable option for patients with severe to profound sensorineural hearing loss due to SH-CNS. In these cases, an adequate pre-operative counseling, explaining the possibility of poor post-operative results and/or the worsening of the outcomes in the following years, is important.

Subepithelial infiltrates in deep anterior lamellar keratoplasty in the presence of a corneal rust ring.

PURPOSE: To report a case of subepithelial infiltrates (SEIs) comprising Langerhans cells, 25 months after deep anterior lamellar keratoplasty (DALK) for keratoconus. METHODS: A case report based on clinical and confocal microscopic examination. RESULTS: A 26-year-old man with progressive keratoconus underwent left DALK. Routine follow-up 25 months postoperatively revealed a rust ring in the graft, scattered SEIs in the edematous donor anterior corneal stroma, and keratic precipitates. The graft cleared after removal of the rust ring and treatment with guttae prednisolone 1%. In vivo confocal microscopy showed accumulation of hyperreflective dendritic structures typical of Langerhans cells at the level of the basal epithelium and the Bowman membrane. DISCUSSION: DALK is an alternative to penetrating keratoplasty in patients with a healthy endothelium. Stromal rejection has been reported up to 41 months postoperatively after DALK. The SEIs and the stromal edema in this case indicated stromal rejection. Increased concentration of antigen-presenting Langerhans cells found on confocal microscopy of the SEIs point to their involvement in the stromal rejection in DALK cases.

Hybrid myxoinflammatory fibroblastic sarcoma/hemosiderotic fibrolipomatous tumor: report of a case providing further evidence for a pathogenetic link.

Myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor are rare, slow-growing soft tissue tumors of the distal extremities with recurrent potential. Recent cytogenetic studies have shown a t(1;10)(p22;q24) or der(10)t(1;10) in combination with aberrations of chromosome 3 in a limited number of cases of both entities. Here we report a case of a 42-year-old female with a soft tissue tumor of the ankle showing hybrid morphologic features of myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor, a der(10)t(1;10), and abnormalities of chromosome 3. This hybrid lesion provides further evidence for a close relationship between these 2 tumor types.

Microsurgical resection of supratentorial cerebral cavernomas.

AIM: More than two thirds of cerebral cavernomas are located supratentorially. The transsulcal approach without excision of the perilesional gliotic parenchyma and simple lesionectomy are keys to surgery on eloquent areas. MATERIAL AND METHODS: We present 11 supratentorial cerebral cavernomas operated between 2003 and 2007 with signs of seizures in six and focal neurological deficit in four cases. The age ranged from 19 years to 69 years with a mean of 40 years and the male/female ratio was 6:5. The mean follow-up was 26 months. RESULTS: All lesions were lobar and the size ranged between 18 and 48 mm. Four were located in eloquent areas and two were deeply seated. Total lesionectomy was performed in all without major complications. A gliotic hemosiderin ring was noted in 7 and resected in 5 of them. Postoperative outcome was improved in all patients with complete seizure control in four. Seizure control was partial in 2 of the cases without any recurrence or residual mass. CONCLUSION: Asymptomatic cerebral cavernomas should be followed with regular MR scans. Symptomatic ones in noneloquent or accessible areas should be resected. Deeply situated cavernomas in eloquent areas should also be resected with the guidance of fMRI and stereotactic marking if available.

Case report: hemosiderotic fibrohistiocytic lipomatous lesion: a clinicopathologic characterization.

BACKGROUND: A hemosiderotic fibrohistiocytic lipomatous lesion, also called hemosiderotic fibrolipomatous tumor, is a rare and recently described fibrolipomatous entity. Initially considered the result of a reactive inflammatory process from trauma or vascular disease, newer evidence suggests it may be neoplastic in origin. CASE REPORT: We report the case of a 56-year-old woman with a painful mass in the dorsal aspect of the foot diagnosed as a hemosiderotic fibrohistiocytic lipomatous lesion. LITERATURE REVIEW: We reviewed all 31 published cases of hemosiderotic fibrohistiocytic lipomatous lesions looking for common clinical, imaging, and histologic patterns. Hemosiderotic fibrohistiocytic lipomatous lesions occur predominantly in the fifth and sixth decades of life (average age, 49.5 years; range, 0.67-74 years). Females predominate 22 to 9. Thirteen of 28 patients had histories of trauma or vasculopathy. Twenty-six of 31 lesions were in the foot. The MRI signal of a hemosiderotic fibrohistiocytic lipomatous lesion follows fat in all sequences. Stranding or septations also frequently are seen. Histologically, the lesions are composed of three main elements in varying proportions: mature adipocytes, spindle cells, and hemosiderin pigment. Ten of 27 resected lesions recurred. Resection types are not reported in many cases. Four of 15 lesions recurred after marginal/intralesional excision, whereas none of three lesions treated by wide excision recurred. PURPOSE AND CLINICAL RELEVANCE: The high recurrence rate may be related to the difficulty in determining intraoperatively that a resection is complete, secondary to the lack of anatomic boundaries such as a pseudocapsule. Any attempt at wide resection must weigh the morbidity of this surgery against that of a recurrence after a resection which seemed complete intraoperatively. There have been no reports of metastasis.

Update in nonneoplastic lung diseases.

CONTEXT: Nonneoplastic lung diseases include a wide range of pathologic disorders from asthma to interstitial lung disease to pulmonary hypertension. Recent advances in our understanding of the pathophysiology of many of these disorders may ultimately impact diagnosis, therapy, and prognosis. It is important for the practicing pathologist to be aware of this new information and to understand how it impacts the diagnosis, treatment, and outcome of these diseases. OBJECTIVE: To update current progress toward elucidating the pathophysiology of pulmonary alveolar proteinosis, idiopathic pulmonary hemosiderosis, and pulmonary arterial hypertension, as well as to present classification systems for pulmonary hypertension, asthma, and interstitial lung disease and describe how these advances relate to the current practice of pulmonary pathology. DATA SOURCES: Published literature from PubMed (National Library of Medicine) and primary material from the authors' institution. CONCLUSIONS: Improved understanding of the pathophysiology of pulmonary alveolar proteinosis, pulmonary hypertension, and idiopathic hemosiderosis may impact the role of the surgical pathologist. New markers of disease may need to be assessed by immunohistochemistry or molecular techniques. The classification systems for interstitial lung disease, asthma, and pulmonary hypertension are evolving, and surgical pathologists should consider the clinicopathologic context of their diagnoses of these entities.

Haemosiderotic fibrohistiocytic lipomatous lesion/tumour of the foot: MRI and histopathology.

A 38-year-old woman presented in 2005 with a fatty swelling over the dorsum of her left foot and was subsequently referred to our institution following initial biopsy for further management. MRI was performed before and after surgery. This demonstrated an ill-defined lesion confined to the subcutaneous tissues on the dorsum of the foot with heterogeneous intermediate and high T1 and T2 signal suggesting a complex mixture of fat and fibrous elements. The lesion recurred following initial surgery in the lateral aspect of the hind foot and along the lateral aspect of the ankle. It demonstrated extremely high signal on T2 fat-saturated sequences along the fibrous elements of the lesion and concentrated in a layer just deep to the dermis, which was mirrored on post-contrast images. A histopathological diagnosis of haemosiderotic fibrohistiocytic lipomatous lesion/tumour (HFLL/T) was made. This is a recently described and rare entity that occurs typically in the subcutaneous tissues of the foot or ankle of middle-aged women. To our knowledge this is the first description of the imaging findings in this lesion.

Hemosiderotic fibrohistiocytic lipomatous lesion: clinical correlation with venous stasis.

Hemosiderotic fibrohistiocytic lipomatous lesion (HFLL) is a recently proposed lipomatous entity. HFLL was originally suggested to be a benign reactive lesion arising due to an antecedent trauma. We report two patients with HFLL who also suffered from chronic vein insufficiency due to varicose involving deep veins of the low limbs. Both patients were middle-aged women with solitary, poorly circumscribed subcutaneous lesions on the lower extremities. Histopathological examination revealed typical features of HFLL. We think that the consistent clinical features such as advanced age, female sex predilection, and specific location along with distinctive histopathological features allow the suggestion that impaired blood circulation, to wit, venous stasis is involved in the pathogenesis of HFLL. We hypothesize that the proliferation of spindled fibroblastic and myofibroblastic cells and capillaries, erythrocyte extravasation, and hemosiderin deposition with lipomatous tissue of HFLL may simply represent an exaggerated tissue response to venous stasis in which elevated venous and capillary pressures, oxygen saturation, and edema stimulate the proliferation of the above mentioned elements and lead to erythrocyte extravasation. A similar histopathological pattern is seen in acroangiodermatitis of Mali and vascular transformation of lymph node sinuses, and these conditions are also associated with impaired blood circulation.

Recurrence of idiopathic pulmonary hemosiderosis in a young adult patient after bilateral single-lung transplantation.

BACKGROUND: Idiopathic pulmonary hemosiderosis (IPH) is a rare disease of unknown etiology characterized by hemoptysis, diffuse pulmonary infiltration, and anemia. Diagnosis requires a detailed clinical history and transbronchial lung biopsy (TLB). METHODS AND RESULTS: A 19-year-old man developed progressive dyspnea, hemoptysis, and anemia. The chest x-rays showed bilateral opacities. IPH was diagnosed on the basis of clinical findings and TLB. The patient was treated with corticosteroidal therapy. His respiratory function worsened, and he underwent lung transplantation in 1997. The pathological examination on native lungs confirmed the previous histologic diagnosis. In 2000, the patient again developed hemoptysis, fever, and hypoxemia. A recurrence of the disease was established by TLB. CONCLUSIONS: This is the first report of recurring IPH. The possibility of recurrent IPH raises the question whether these patients should be disqualified from lung transplantation. This question is unanswerable because incidence of recurrence, time course, and impact on the graft function are presently unknown and unpredictable.