Quantitative electroencephalography in cerebral amyloid angiopathy.

OBJECTIVE: We investigated whether quantitative electroencephalography (qEEG) correlates with cognition and cortical superficial siderosis (cSS) in cerebral amyloid angiopathy. METHODS: We included patients with sporadic (sCAA) and hereditary Dutch-type CAA (D-CAA). Spectral measures and the phase lag index (PLI) were analyzed on qEEG. Cognition was assessed with the MoCA and cSS presence was scored on 3T-MRI. Linear regression analyses were performed to investigate these qEEG measures and cognition. Independent samples T-tests were used to analyze the qEEG measure differences between participants with and without cSS. RESULTS: We included 92 participants (44 D-CAA; 48 sCAA). A lower average peak frequency (ß[95 %CI] = 0.986[0.252-1.721]; P = 0.009) and a higher spectral ratio (ß[95 %CI] = -0.918[-1.761--0.075]; P = 0.033) on qEEG correlated with a lower MoCA score, irrespective of a history of symptomatic intracerebral hemorrhage (sICH). The PLI showed no correlation to the MoCA. qEEG slowing was not different in those with or without cSS. CONCLUSIONS: Spectral qEEG (but not PLI) reflects cognitive performance in patients with CAA with and without a history of sICH. We found no association between qEEG slowing and cSS. SIGNIFICANCE: qEEG could be a valuable biomarker, especially in challenging cognitive testing situations in CAA, and a potential predictive tool in future studies.

Subarachnoid extension of lobar hemorrhage on acute/subacute MRI is associated with cerebral amyloid angiopathy criteria.

Subarachnoid hemorrhage extension (SAHE) in the acute phase of cerebral amyloid angiopathy (CAA)-related lobar hemorrhage (LH) assessed by CT is very frequent. Recently, SAHE, together with finger-like projections on CT and ApoE4, has been used in a prediction model for histopathologically proven CAA showing excellent discrimination. Our aim was to analyze SAHE on MRI in the acute and subacute phase of LH in patients with and without associated hemorrhagic features supportive of CAA (i.e. chronic LH, cortical superficial siderosis [CSS], and strictly lobar cerebral microbleeds [CMB]). We retrospectively studied SAHE on MRI performed in the acute and subacute phase (within 21 days) in a cohort of consecutive patients with acute LH recruited between January 2012 and April 2018. Sixty-eight acute LH patients (35 men and 33 women, mean age 74 [range 50-89]) were analyzed. Mean delay between symptom onset and MRI was 3.8 days, and 32 patients underwent MRI within 24 h. Based on MRI, 51 patients were classified as probable CAA and 17 patients without probable CAA. Both groups were comparable regarding age, sex, time of MRI performance, MRI field strength, and acute LH volume. Overall, SAHE was observed in 46 (68%) patients, including 39 (76%) patients with probable CAA and 7 (41%) patients without probable CAA (p = 0.015). SAHE presence was also associated with larger LH volumes. During the work-up in the acute/subacute phase of patients with acute LH, in addition to T2*-weighted imaging in search for other hemorrhagic features (chronic LH, CSS, or lobar CMB) evoking probable underlying CAA etiology, search for SAHE on adapted MRI sequences (FLAIR and T2*-weighted imaging) seems to be interesting because of the association with the presence of probable CAA criteria.

Bilateral Vestibulopathy Documented by Video Head Impulse Tests in Superficial Siderosis.

OBJECTIVE: Superficial siderosis (SS) of the CNS is associated with cerebellar ataxia, sensorineural hearing loss, and pyramidal symptoms, which result from iron depositions on CNS surfaces. SS can produce bilateral vestibulopathy as the vestibulo-cochlear nerve is particularly vulnerable. To our knowledge, however, vestibular dysfunction in SS has not been reported thoroughly in the literature. Here, we describe a case of bilateral vestibulopathy, documented quantitatively by the video head impulse test (vHIT), in a patient with SS. PATIENT: A 60-year-old man presented with slowly progressing bilateral hearing loss, oscillopsia, and a severe gait disturbance that worsened in the dark. INTERVENTION: After noticing deficits in the bedside head impulse test in all six semicircular canals, the patient underwent vHIT and brain MRI. MAIN OUTCOME MEASURE: MRI demonstrated a rim of hypointensities and signal losses in T2-weighted and gradient echo images around the cerebellum, brainstem, and vestibulo-cochlear nerve, which were compatible with an SS diagnosis. In addition, vHIT revealed reduced vestibule-ocular reflex (VOR) gains, and abnormal catch-up saccades (both covert and overt saccades) in all semicircular canals. RESULTS: The vHIT showed impaired VOR gains that were 0.55, 0.59, and 0.45 in the horizontal, anterior, and posterior canals, respectively. CONCLUSION: SS may result in chronic bilateral vestibulopathy with SNHL. Bilateral vestibulopathy originated peripherally in our participant, without cerebellar dysfunctions such as those reported in the literature. vHIT findings have not been previously reported in patients with SS, and our study suggests that vHIT is a useful tool to document vestibular dysfunction.

[Comparison of welder's pneumoconiosis with silicosis and follow-up study of welder's pneumoconiosis].

OBJECTIVE: To study the character of welder's pneumoconiosis on CT, pathology, and lung function. METHODS: To contrast 185 welder's pneumoconiosis and 115 silicosis on CT, pathology, and clinical characters which were diagnosed between Jan 2008 and Dec 2013. Chest X-ray and lung function of 39 welder's pneumoconiosis patients were followed up after diagnosed 4~6 years later. RESULTS: Average age and working years of welder's pneumoconiosis were 36.7 and 11.5, less than silicosis patients 58.8 and 22.1, respectively (P<0.05). Of all 185 welder's pneumoconiosis 98.4% were of stage I and no stage III, while in silicosis group stage I, stage II and stage III were 56.5%, 22.6% and 20.9%, respectively. The ratio differences between the two groups were statistically significant,P<0.05. 82.7% of welder's pneumoconiosis patients were observed pathologically moderate or above dust deposition in lung tissue while interstitial fibrosis level was just mild (97.6% patients) or no fibrosis (2.4% patients). By contrast, 60.0% silicosis patients pathologically showed moderate or above dust deposition while 77.8% were of moderate or above fibrosis. CT findings in welder' s pneumoconiosis were diffuse branching linear structure (38.9%), low density consistent size centrilobular micronodules (19.5%), or both (30.8%). Poorly-defined ground-glass attenuation centrilobular micronodules or widely ground glass shadow were observed in 6.4% welder's pneumoconiosis patents. 30.8% patients failed to reach the original stage when 39 welder's pneumoconiosis followed up chest radiograph. CONCLUSION: Changes in welder's lung caused by welding fume were not only siderosis, but also interstitial fibrosis.

Functional and high resolution retinal imaging assessment in a case of ocular siderosis.

PURPOSE: To report new findings in a case of ocular siderosis explored by high resolution angiography and adaptive optics (AO). METHODS: We report data on a 40-year-old man with an intraocular foreign body (IOFB) embedded in the sclera after hammering. RESULTS: Nine months after this accident, the patient presented with full-field electroretinogram (FF-ERG) abnormalities. Subsequent IOFB extraction was performed. One month after the surgery, high resolution angiography showed for the first time small iron particles all over the inner retinal surface. Spreading of these deposits was followed by inflammatory prepapillary new vessels and venous retinal vasculatis, which spontaneously resolved within a few months. ERG responses became slightly electronegative at this time. Clearance of the iron particles was followed over a year with AO and ERG recording. AO revealed an arterial tropism with a decrease in the amount of particles overtime, which may be consistent with macrophagic activity. CONCLUSION: High resolution angiography and AO are new tools, combined with electrophysiology, to better understand ocular siderosis pathophysiology.

Auditory profile in superficial siderosis of the central nervous system: a prospective study.

OBJECTIVE: To identify auditory pathology resulting from superficial siderosis of the central nervous system (SSCN), auditory site of lesion, and a clinical profile for differential diagnosis and development of recommendations. STUDY DESIGN: Prospective study. SETTING: Academic clinical center. PATIENTS: Ten participants with SSCN (the largest prospective evaluation of audiologic status reported to date). INTERVENTION(S): Demographics, clinical characteristics and history, audiometric evaluation, and Tinnitus Handicap Inventory (THI). MAIN OUTCOME MEASURE(S): Type and degree of hearing loss, relationship to clinical course of SSCN, and expected results based on age and sex. RESULTS: Sensorineural hearing loss (SNHL) is the most common symptom in SSCN (100%). Tinnitus (100%), imbalance (80%), and gait disorder (80%) were also frequently reported. Hearing loss is typically bilateral, asymmetric, progressive, sloping, and exceeds expected hearing loss related to age and sex. Hearing loss may be cochlear and/or retrocochlear in origin. Decreased word recognition is possible, and traditional amplification may offer limited benefit. CONCLUSION: We observed significant audiometric findings in all participants. SSCN variably and pathologically targets the auditory system without regard for duration of disorder. A long asymptomatic phase and lack of predictive relationship between duration and severity of hearing loss makes suspicion of SSCN based solely on audiometric battery difficult; however, asymmetric hearing loss exceeding expectations, particularly with history of head trauma or previous neurosurgical procedure, should raise a red flag and trigger further medical evaluation including MRI. Diagnosis of SSCN may alter expectations for audiologic prognosis and is a critical component for comprehensive management of SSCN patients.

Superficial siderosis is a warning sign for future intracranial hemorrhage.

Supratentorial superficial siderosis (SS) is a frequent imaging marker of cerebral amyloid angiopathy (CAA). It is most probably caused by focal subarachnoid hemorrhages (fSAHs). Based on single-case observations, it has been proposed that such fSAHs might be a predisposing factor for future intracranial hemorrhage. Here we tested the hypothesis if a SS as a residue of fSAHs must be regarded as a warning sign for future intracranial hemorrhage. Fifty-one consecutive patients with SS and no apparent cause other than possible or probable CAA were identified through a database search and followed-up for a median interval of 35.3 months (range 6-120 months). Main outcome measures were rate and location of new intracranial hemorrhages. Twenty-four patients (47.1 %) had experienced any new intracranial hemorrhage, 18 patients (35.3 %) had an intracerebral hemorrhage (ICH), and in 13 of them (25.5 %), the hemorrhage was located at the site of pre-existing siderosis. Six patients (11.7 %) had developed a new subarachnoid hemorrhage (SAH), four of them at the site of siderosis. Patients with SS are at substantial risk for subsequent intracranial hemorrhage. SS can be considered a warning sign of future ICH or SAH, which frequently occur adjacent to pre-existing SS. Prospective studies are needed to confirm these findings.

[Ocular siderosis]. / Siderosos bulbi--caz clinic.

We show a clinical case of siderosis bulbi with absolute secondary glaucoma. The initial diagnosis was primary open angle glaucoma in both eyes, and the patient was treated with eye drops for 4 years. After reassessment of anamnesis, clinical and paraclinical investigations we find that one eye is normal and the real diagnosis in the involved eye.

Superficial siderosis of the central nervous system manifested with seizures.

Superficial siderosis of the central nervous system (CNS) is caused by repeated hemorrhage into the subarachnoid space with resultant hemosiderin deposition in the subpial layers of the brain and spinal cord. Progressive ataxia and hearing impairment are the most common manifestations of the disorder. We describe a male patient admitted to our hospital for recurrent seizures over the past 3 months. He was diagnosed eventually as having superficial siderosis of the CNS through brain MRI; however, he presented with only mild hearing impairment without any cerebellar deficits. Seizures can be the major presentation of the superficial siderosis.

Superficial siderosis in the general population.

BACKGROUND: Superficial siderosis is a rare radiologic diagnosis of hemosiderin deposition in subpial brain layers. In case studies, an association between superficial siderosis and cerebral amyloid angiopathy (CAA) has been described. Also, a potential role of superficial siderosis in Alzheimer disease (AD) was hypothesized. All previously reported cases of superficial siderosis were detected because of overt clinical symptoms. We studied the occurrence of superficial siderosis on brain MRI in a general population of nondemented elderly. METHODS: In 1,062 persons (mean age 69.6 years) from the population-based Rotterdam Scan Study, we performed T2*-weighted MRI to assess the presence of superficial siderosis. Furthermore, the presence, number, and location of cerebral microbleeds were rated, as lobar microbleeds are thought to be indicative of CAA. RESULTS: We found that superficial siderosis was present in 7 (0.7%) individuals, all of whom had cerebral microbleeds in lobar locations. Furthermore, in all 7 persons, microbleeds were located in close vicinity to superficial siderosis. CONCLUSIONS: Our results provide further indirect support for the presumed link between superficial siderosis and cerebral amyloid angiopathy (CAA). Whether superficial siderosis may be a marker for severity or worse prognosis of CAA needs to be further evaluated in longitudinal follow-up.

Superficial siderosis of central nervous system mimicking multiple sclerosis.

INTRODUCTION: Superficial siderosis of the central nervous system is a neurologic disorder mainly characterized by cerebellar involvement, myelopathy, neurosensory hearing loss, and possibly progressive cognitive impairment. Root avulsion due to traumatic plexus injury has been recognized as an extremely rare cause of hemosiderin deposition on leptomeninges and subpial layers of brain and spinal cord parenchyma. CASE REPORT: A 49-year-old man presented with progressively evolving ataxia and spastic paraparesis. CSF oligoclonal bands were indicative of an underlying inflammatory process and raised the possibility of a demyelinating disorder. However, spinal cord and brain MRI revealed hemosiderin deposition along the entire neuraxis. A rigorous electrophysiologic study confirmed a functional impairment in many different levels of the nervous system. CONCLUSION: The demonstration of CSF oligoclonal bands in the reported patient implies that inflammation might be involved in the pathogenesis of superficial siderosis. The diagnosis of this newly recognizable entity needs a high clinical suspicion, but further research is needed to fully elucidate the involved mechanisms.

Superficial siderosis: a potential diagnostic marker of cerebral amyloid angiopathy in Alzheimer disease.

BACKGROUND AND PURPOSE: Superficial siderosis of the central nervous system results from chronic bleeding in the superficial layers of the cortex and spinal cord. In cerebral amyloid angiopathy (CAA), there is amyloid deposition in meningeal and meningo-cortical arteries and capillaries, predisposing them to rupture. CAA is frequently associated with Alzheimer disease (AD). METHODS: We report a series of 3 AD patients with MRI evidence of superficial siderosis. Two had neuropathological examination confirming superficial siderosis, AD, and CAA. CONCLUSIONS: Superficial siderosis should be recognized within the spectrum of AD with CAA and considered as a possible antemortem diagnostic feature.

Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction.

BACKGROUND: In thalassemia major (TM), severe cardiac siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial siderosis, but has not been prospectively examined in severe myocardial siderosis. METHODS: T2* cardiovascular magnetic resonance (CMR) was performed in 167 TM patients receiving standard subcutaneous deferoxamine monotherapy, and 22 had severe myocardial siderosis (T2* < 8 ms) with impaired left ventricular (LV) function. Fifteen of these patients received combination therapy with subcutaneous deferoxamine and oral deferiprone with CMR follow-up. RESULTS: At baseline, deferoxamine was prescribed at 38 +/- 10.2 mg/kg for 5.3 days/week, and deferiprone at 73.9 +/- 4.0 mg/kg/day. All patients continued both deferiprone and deferoxamine for 12 months. There were no deaths or new cardiovascular complications. The myocardial T2* improved (5.7 +/- 0.98 ms to 7.9 +/- 2.47 ms; p = 0.010), with concomitant improvement in LV ejection fraction (51.2 +/- 10.9% to 65.6 +/- 6.7%; p < 0.001). Serum ferritin improved from 2057 (CV 7.6%) to 666 (CV 13.2%) microg/L (p < 0.001), and liver iron improved (liver T2*: 3.7 +/- 2.9 ms to 10.8 +/- 7.3 ms; p = 0.006). CONCLUSION: In patients with severe myocardial siderosis and impaired LV function, combined chelation therapy with subcutaneous deferoxamine and oral deferiprone reduces myocardial iron and improves cardiac function. This treatment is considerably less onerous for the patient than conventional high dose continuous subcutaneous or intravenous deferoxamine monotherapy, and may be considered as an alternative. Very prolonged tailored treatment with iron chelation is necessary to clear myocardial iron, and alterations in chelation must be guided by repeated myocardial T2* scans. TRIAL REGISTRATION: This trial is registered as NCT00103753.

Effects of colloidal iron overload on renal and hepatic siderosis and the femur in male rats.

Genetic hemochromatosis is an iron overload disorder, and osteopenic and osteoporotic. Femoral neck bone mineral density (BMD) appears to fall with rising hepatic iron concentrations. A critical role for iron in mediating tissue injury is played via hydroxyl radical formation in nephrotoxicity. We investigated the effects of a colloidal iron overload on renal function, organ siderosis, and femoral bone in male rats. Iron overload reduced body growth, and increased the weights of the liver and spleen. Marked deposition of iron was noted in liver and kidney. Activities of lactate dehydrogenase and alkaline phosphatase were decreased, and the concentrations of blood urea nitrogen and creatinine were increased with the reduction in plasma calcium and inorganic phosphorus levels, i.e. functions of the liver and kidney might be affected by reactive oxygen species such as the superoxide radical, H2O2, and the hydroxyl radical produced by overloaded iron. Damage to the proximal tubular epithelial cells of the kidney and a loss of connectivity of cancellous bone in the epiphysis and of trabecular bone in the metaphysis of the distal femur were observed in iron-overloaded rats with a reduction of femoral bone mineral density, i.e. reabsorption of calcium from the proximal tubular epithelial cells of the kidney might be affected and urinary discharge of calcium might be elevated. It was suggested that iron overload gave rise to osteoporosis combined with renal dysfunction and liver iron overload syndrome.