Hemorrhagic Transformation in Noncardioembolic Acute Ischemic Stroke: MRI Analysis From PACIFIC-STROKE.

BACKGROUND: In the phase 2 PACIFIC-STROKE trial (Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following Acute Noncardioembolic Stroke), asundexian, an oral factor XIa inhibitor, did not increase the risk of hemorrhagic transformation (HT). In this secondary analysis, we aimed to investigate the frequency, types, and risk factors of HT on brain magnetic resonance imaging (MRI). METHODS: This was a secondary analysis of the PACIFIC-STROKE trial. Patients with mild-to-moderate acute noncardioembolic ischemic stroke were randomly assigned to asundexian or placebo plus guideline-based antiplatelet therapy. Brain MRIs were required at baseline (≤120 hours after stroke onset) and at 26 weeks or end-of-study. HT was defined using the Heidelberg classification and classified as early HT (identified on baseline MRI) or late HT (new HT by 26 weeks) based on iron-sensitive sequences. Multivariable logistic regression models were used to test factors that are associated with early HT and late HT, respectively. RESULTS: Of 1745 patients with adequate baseline brain MRI (mean age, 67 years; mean National Institutes of Health Stroke Scale score, 2.8), early HT at baseline was detected in 497 (28.4%). Most were hemorrhagic infarctions (hemorrhagic infarction type 1: 15.2%; HI2: 12.7%) while a few were parenchymal hematomas (parenchymal hematoma type 1: 0.4%; parenchymal hematoma type 2: 0.2%). Early HT was more frequent with longer symptom onset-to-MRI interval. Male sex, diabetes, higher National Institutes of Health Stroke Scale large (>15 mm) infarct size, cortical involvement by infarct, higher number of acute infarcts, presence of chronic brain infarct, cerebral microbleed, and chronic cortical superficial siderosis were independently associated with early HT in the multivariable logistic regression model. Of 1507 with follow-up MRI, HT was seen in 642 (42.6%) overall, including 361 patients (23.9%) with late HT (new HT: 306; increased grade of baseline HT: 55). Higher National Institutes of Health Stroke Scale, large infarct size, cortical involvement of infarct, and higher number of acute infarcts predicted late HT. CONCLUSIONS: About 28% of patients with noncardioembolic stroke had early HT, and 24% had late HT detectable by MRI. Given the high frequency of HT on MRI, more research is needed on how it influences treatment decisions and outcomes.

Surgical closure of spinal cerebrospinal fluid leaks improves symptoms in patients with superficial siderosis.

BACKGROUND AND PURPOSE: Spinal cerebrospinal fluid (CSF) leaks may cause a myriad of symptoms, most common being orthostatic headache. In addition, ventral spinal CSF leaks are a possible etiology of superficial siderosis (SS), a rare condition characterized by hemosiderin deposits in the central nervous system (CNS). The classical presentation of SS involves ataxia, bilateral hearing loss, and myelopathy. Unfortunately, treatment options are scarce. This study was undertaken to evaluate whether microsurgical closure of CSF leaks can prevent further clinical deterioration or improve symptoms of SS. METHODS: This cohort study was conducted using data from a prospectively maintained database in two large spontaneous intracranial hypotension (SIH) referral centers in Germany and Switzerland of patients who meet the modified International Classification of Headache Disorders, 3rd edition criteria for SIH. Patients with spinal CSF leaks were screened for the presence of idiopathic infratentorial symmetric SS of the CNS. RESULTS: Twelve patients were included. The median latency between the onset of orthostatic headaches and symptoms attributed to SS was 9.5 years. After surgical closure of the underlying spinal CSF leak, symptoms attributed to SS improved in seven patients and remained stable in three. Patients who presented within 1 year after the onset of SS symptoms improved, but those who presented in 8-12 years did not improve. We could show a significant association between patients with spinal longitudinal extrathecal collections and SS. CONCLUSIONS: Long-standing untreated ventral spinal CSF leaks can lead to SS of the CNS, and microsurgical sealing of spinal CSF leaks might stop progression and improve symptoms in patients with SS in a time-dependent manner.

Clinical and neuroimaging precursors in cerebral amyloid angiopathy: impact of the Boston criteria version 2.0.

BACKGROUND AND PURPOSE: Although the Boston criteria version 2.0 facilitates the sensitivity of cerebral amyloid angiopathy (CAA) diagnosis, there are only limited data about precursor symptoms. This study aimed to determine the impact of neurological and imaging features in relation to the time of CAA diagnosis. METHODS: Patients diagnosed with probable CAA according to the Boston criteria version 1.5, treated between 2010 and 2020 in our neurocentre, were identified through a keyword search in our medical database. Neuroimaging was assessed using Boston criteria versions 1.5 and 2.0. Medical records with primary focus on the clinical course and the occurrence of transient focal neurological episodes were prospectively evaluated. RESULTS: Thirty-eight out of 81 patients (46.9%) exhibited transient focal neurological episodes, most often sensory (13.2%) or aphasic disorders (13.2%), or permanent deficits at a mean time interval of 31.1 months (SD ±26.3; range 1-108 months) before diagnosis of probable CAA (Boston criteria version 1.5). If using Boston criteria version 2.0, all patients receiving magnetic resonance imaging (MRI) met the criteria for probable CAA, and diagnosis could have been made on average 44 months earlier. Four patients were younger than 50 years, three of them with supporting pathology. Cognitive deficits were most common (34.6%) at the time of diagnosis. CONCLUSIONS: Non-haemorrhagic MRI markers enhance the sensitivity of diagnosing probable CAA; however, further prospective studies are proposed to establish a minimum age for inclusion. As the neurological overture of CAA may occur several years before clinical diagnosis, early clarification by MRI including haemosensitive sequences are suggested.

Duropathy as a rare motor neuron disease mimic: from bibrachial amyotrophy to infratentorial superficial siderosis.

BACKGROUND: Bibrachial amyotrophy associated with an extradural CSF collection and infratentorial superficial siderosis (SS) are rare conditions that may occasionally mimic ALS. Both disorders are assumed to be due to dural tears. CASE PRESENTATION: A 53-year-old man presented with a 7-year history of slowly progressive asymmetric bibrachial amyotrophy. Initially, a diagnosis of atypical motor neuron disease (MND) was made. At re-evaluation 11 years later, upper limb wasting and weakness had further progressed and were accompanied by sensorineural hearing loss. MRI of the brain and spine demonstrated extensive supra- and infratentorial SS (including the surface of the whole spinal cord) as well as a ventral longitudinal intraspinal fluid collection (VLISFC) extending along almost the entire thoracic spine. Osteodegenerative changes were observed at C5-C7 level, with osteophytes protruding posteriorly. The bony spurs at C6-C7 level were hypothesized to have lesioned the dura, causing a CSF leak and thus a VLISFC. Review of the MRI acquired at first evaluation showed that the VLISFC was already present at that time (actually beginning at C7 level), whereas the SS was not. 19 years after the onset of upper limb weakness, the patient additionally developed parkinsonism. Response to levodopa, brain scintigraphy with 123I-ioflupane and brain MRI with nigrosome 1 evaluation were consistent with idiopathic Parkinson's disease (PD). On the latest follow-up 21 years after symptom onset, the VLISFC was unchanged, as were upper arm weakness and wasting. CONCLUSIONS: Based on the long-term follow-up, we could establish that, while the evidence of the VLISFC was concomitant with the clinical presentation of upper limb amyotrophy and weakness, the radiological signs of SS appeared later. This suggests that SS was not per se the cause of the ALS-like clinical picture, but rather a long-term sequela of a dural leak. The latter was instead the causative lesion, giving rise to a VLISFC which compressed the cervical motor roots. Dural tears can actually cause several symptoms, and further studies are needed to elucidate the pathophysiological correlates of "duropathies". Finally, as iron metabolism has been implicated in PD, the co-occurrence of PD with SS deserves further investigation.

Post-transfusion severe headache in a patient with thalassemia with superficial siderosis of the central nervous system: a case report and literature review.

BACKGROUND: Patients with severe thalassemia may experience adverse effects from transfusion such as fever, rash, and iron overload after long-term transfusion therapy. Severe headaches as a side effect of blood transfusion in patients with thalassemia are not commonly observed, especially when combined with superficial siderosis of the central nervous system, which is easily misdiagnosed and requires excessive examination and treatment. CASE PRESENTATION: A 31-year-old woman was admitted with severe headache and vomiting over 3 days following blood transfusion. She was diagnosed with intermediate α-thalassemia at 2 years of age and had a history of irregular blood transfusions. Physical examination revealed horizontal nystagmus with no other abnormal neurological signs. Magnetic resonance (MR) imaging, MR venography, MR arteriography, and cerebrospinal fluid analysis were normal. However, susceptibility-weighted imaging showed abnormal signals in the bilateral and fourth ventricles. Initial antibiotics, antivirals, decompression of intracranial pressure, iron chelation, and symptomatic treatments were administered; subsequently, small intermittent blood transfusions were cautiously administered for severe anemia. The patient's headache was gradually relieved, and she was discharged on day 9. At the 5-month follow-up, the patient's headache recurred following another transfusion. CONCLUSIONS: Severe post-transfusion headache in patients with thalassemia has not been fully recognized and is easily misdiagnosed, leading to excessive examination and treatment. Understanding the clinical features of transfusion-related headaches can help identify this complication, but the exact pathophysiological mechanism requires further research.

Progressive superficial siderosis despite complete remission of intracranial hypotension symptoms following epidural patching: Case report.

Spontaneous intracranial hypotension (SIH) commonly results from ventral spinal cerebrospinal fluid (CSF) leaks and epidural patches are advocated as first-line treatment. Complications such as superficial siderosis can arise but have previously been reported only in the context of long-term persistent, ongoing, CSF leak and SIH. We report a case of a patient with SIH from a ventral spinal CSF leak that was treated with epidural patching and experienced complete resolution of SIH. Four years later SIH symptoms recurred, and brain magnetic resonance imaging unexpectedly showed the interval accumulation of hemosiderin pigmentation on the cerebellum and brainstem during the period when the patient was without symptoms of SIH. This case uniquely demonstrates the progression of superficial siderosis despite the apparent resolution of SIH. Our findings suggest two divergent pathophysiological outcomes from spinal ventral dural tear: (1) CSF loss causing SIH; and (2) persistent low-level bleeding arising from the spinal dural tear leading to superficial siderosis. These divergent pathophysiologies had a discordant response to epidural patching. Epidural patching successfully treated the SIH but did not prevent the progression of superficial siderosis, indicating that some patients may require more than epidural patching despite symptom resolution. This case highlights the need for post-treatment monitoring protocols in patients with ventral spinal CSF leaks and SIH and raises important questions about the adequacy of epidural patching in certain SIH cases arising from ventral spinal CSF leak.

Tumefactive cerebral amyloid angiopathy - related inflammation.

INTRODUCTION: Cerebral amyloid angiopathy-related inflammation (CAA-ri) derives from inflammatory response to ß-amyloid (Aß) protein deposition within the cerebral blood vessel walls. We report a case that accentuates those clinical and imaging features that can contribute to raise suspicion for the condition and lead to early treatment initiation. CASE PRESENTATION: A 72-year-old man was referred with one-month history of cognitive decline along with behavioral alterations. Brain MRI showed fluid attenuated inversion recovery (FLAIR) asymmetrical multifocal white matter hyperintensities (WMHs) along with multiple cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS) on T2*-weighted gradient-recalled echo (T2*-GRE) images. Metabolic, infectious, and neoplastic causes were excluded, and subsequently corticosteroids were administered to the patient resulting in clinical recovery. Imaging on follow-up disclosed remission of WMHs, while CMBs load increased significantly. DISCUSSION: Clinical neurologists' acquaintance with the clinical and imaging features of CAA-ri allows prompt diagnosis and medication initiation, that is essential for a conceivably treatable condition.

Correlation between plasma biochemical parameters and cardio-hepatic iron deposition in thalassemia major patients.

INTRODUCTION: Major Thalassemia patients suffer from iron overload and organ damage, especially heart and liver damage. Early diagnosis and treatment with a chelator can reduce the complications and mortality of iron overload. Therefore, we aimed to investigate the biochemical and hematological predictors as an alternative and indirect indicator of iron deposition in heart and liver cells in comparison with the MRI T2* method as the gold standard. MATERIAL AND METHOD: MRI T2* was evaluated in the heart and liver tissues of 62 major beta-thalassemia patients undergoing regular transfusion and chelator therapy. Biochemical and hematological factors were also measured, including serum ferritin, serum electrolytes, liver enzymes, hemoglobin, blood glucose, and serum magnesium. The correlation between these factors was assessed using statistical evaluations. RESULT: Serum ferritin had a positive and significant correlation with liver siderosis based on MRI T2* (p-value = .015), and no significant association was observed with cardiac siderosis (p-value = .79). However, there was a significant positive correlation between cardiac iron deposition and fasting blood sugar level (p-value = -.049), and plasma level of liver enzymes (alanine aminotransferase (ALT) (p-value = .001), aspartate aminotransferase (AST ((p-value = .01)). Moreover, there was a significant negative correlation between cardiac iron overload and plasma magnesium level (p-value = .014). According to MRI T2*, there was no significant correlation between cardiac and hepatic iron overload (p value = .36). CONCLUSION: An increase in blood sugar or liver enzymes and a decrease in serum magnesium was associated with an increase in cardiac iron overload based on MRI T2*. Liver iron overload based on MRI T2* had a significant correlation with serum ferritin.

Demystifying the role of magnetic resonance in identifying intraocular foreign bodies: a case of ocular siderosis.

BACKGROUND: Ocular siderosis (OS) is a significant cause of visual loss due to retained ferrous intraocular foreign bodies (IOFB). Despite its rarity, OS can lead to severe visual impairment if not promptly diagnosed and treated. This case is notable due to the occult nature of the IOFB, which was undetected by standard imaging modalities, emphasizing the critical role of magnetic resonance imaging (MRI) in such scenarios. CASE PRESENTATION: A 51-year-old Caucasian male presented with progressive vision loss in his right eye over 20 days. Best corrected visual acuity (BCVA) was 20/1000 in the right eye and 20/20 in the left eye. Intraocular pressure (IOP) was 9 mmHg in both eyes. Slit-lamp examination revealed a small linear corneal wound and an iris defect in the right eye, along with a cataract featuring brownish deposits on the anterior capsule. The left eye was normal. Fundus examination of the right eye was hindered by media opacities. Ultrasonography showed a flat retina and choroid with no detectable IOFB. Despite a strong clinical suspicion of OS, computed tomography (CT) did not detect any IOFB. MRI subsequently identified an artifact in the inferior sectors of the right eye, indicative of a metallic IOFB. Surgical intervention involved a 23-gauge vitrectomy, phacoemulsification, IOFB removal and silicon oil (SO) tamponade resulting in a fully restored VA of 20/20 and normal IOP one month post-operation. SO was removed 2 months later. The retina remained adherent with no PVR development, and optical coherence tomography (OCT) scans showed a normal macula. CONCLUSIONS: This case underscores the importance of considering OS in patients with unexplained vision loss and history of ocular trauma, even when initial imaging fails to detect an IOFB. MRI proved crucial in identifying the IOFB, highlighting its value in the diagnostic process. Early detection and surgical removal of IOFBs are essential to prevent irreversible visual damage. This case demonstrates that MRI should be employed when CT and ultrasonography are inconclusive, ensuring accurate diagnosis and timely intervention to preserve vision.

Treatment of Iron-Induced Cutaneous Hyperpigmentation With Energy-Based Devices.

OBJECTIVES: Iatrogenic cutaneous siderosis is a well-recognized dermatologic complication after parenteral iron infusion. The condition manifests as discrete, hyperpigmented patches near the site of injection. Most cases do not resolve spontaneously, leading to significant aesthetic and psychological distress to patients. A recent case of iatrogenic cutaneous siderosis at our institution prompted a systematic review of the efficacy of energy-based devices previously reported in the treatment of this condition. METHODS: PubMed and Cochrane databases were searched for all peer-reviewed articles published using the following search terms: "iron OR heme OR hemosiderosis OR siderosis" and "hyperpigmentation OR staining OR tattoo." Articles reporting on energy-based devices in the treatment of iron-induced hyperpigmentation were included. RESULTS: A total of seven articles and 54 total patients were included in this review. All patients, including the patient treated at our institution, were female, with an average age of 44 years. Hyperpigmentation was most commonly associated with intravenous iron infusion (48/54, 89%), on the arm or forearm (44/54, 81%), and used for the treatment of underlying iron deficiency anemia (54/54, 100%). The application of six different nanosecond or picosecond quality-switched laser systems was reported in the treatment of cutaneous siderosis, with wavelengths ranging from 532 to 1064 nm. Spot sizes varied between 2 and 7 mm, with energy fluences spanning 0.5-40 J/cm2 depending on both the device and spot size. Outcomes were measured after an average of 5.4 laser treatments and 10.4 months, with over half of all reported patients experiencing complete clearance (27/50, 54%). Our patient received treatment in three test areas with picosecond alexandrite 785 nm, nanosecond Nd:YAG 532 nm, and picosecond Nd:YAG 532 nm devices. The nanosecond Nd:YAG 532 nm treated area demonstrated the greatest improvement, and the entire arm was subsequently treated with this device. CONCLUSIONS: Despite the often intractable nature of iatrogenic cutaneous siderosis, laser surgery is a reasonable and safe treatment modality for patients seeking cosmetic improvement of this dyschromia. Dermatologists should be aware of this entity and the efficacy of the energy-based devices currently in our armamentarium. A combination approach may need to be utilized with different wavelengths and pulsed widths to target iron pigment in both dermal and subcutaneous layers.

Non-hemorrhagic imaging markers of cerebral amyloid angiopathy in memory clinic patients.

INTRODUCTION: The Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) incorporated non-hemorrhagic imaging markers. Their prevalence and significance in patients with cognitive impairment remain uncertain. METHODS: We studied 622 memory clinic patients with available magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers. Two raters assessed non-hemorrhagic markers, and we explored their association with clinical characteristics through multivariate analyses. RESULTS: Most patients had mild cognitive impairment; median age was 71 years and 50% were female. Using the v2.0 criteria, possible or probable CAA increased from 75 to 383 patients. Sixty-eight percent of the sample had non-hemorrhagic CAA markers, which were independently associated with age (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.01-1.07), female sex (OR = 1.68, 95% CI = 1.11-2.54), and hemorrhagic CAA markers (OR = 2.11, 95% CI = 1.02-4.35). DISCUSSION: Two-thirds of patients from a memory clinic cohort had non-hemorrhagic CAA markers, increasing the number of patients meeting the v2.0 CAA criteria. Longitudinal approaches should explore the implications of these markers, particularly the hemorrhagic risk in this population. HIGHLIGHTS: The updated Boston criteria for cerebral amyloid angiopathy (CAA) now include non-hemorrhagic markers. The prevalence of non-hemorrhagic CAA markers in memory clinic patients is unknown. Two-thirds of patients in our memory clinic presented non-hemorrhagic CAA markers. The presence of these markers was associated with age, female sex, and hemorrhagic CAA markers. The hemorrhagic risk of patients presenting these type of markers remains unclear.

[Analysis of the prevalence of anticoagulant therapy in patients with cognitive disorders and cerebral amyloid angiopathy (CAA)]. / Analyse zur Häufigkeit einer gerinnungshemmenden Medikation bei Patientinnen mit kognitiven Störungen und zerebraler Amyloidangiopathie (CAA).

OBJECTIVES: To investigate the prevalence of coincident anticoagulation in patients with cognitive disorders and possible or probable cerebral amyloid angiopathy (CAA) as well as the relationship between the presence of oral anticoagulation and CAA-specific lesion load. MATERIALS AND METHODS: Patients with subjective cognitive decline (SCD), amnestic and non-amnestic mild cognitive impairment (aMCI/naMCI), Alzheimer's disease (AD), mixed dementia (MD) and vascular dementia (VD) who presented to our outpatient dementia clinic between February 2016 and October 2020 were included in this retrospective analysis. Patients underwent cranial magnetic resonance imaging (MRI). MRI data sets were analyzed regarding the presence of CAA-related MRI biomarkers to determine CAA prevalence. Presence of anticoagulant therapy was determined by chart review. RESULTS: Within the study period, 458 patients (209 male, 249 female, mean age 73.2 ± 9.9 years) with SCD (n = 44), naMCI (n = 40), aMCI (n = 182), AD (n = 120), MD (n = 68) and VD (n = 4) were analyzed. A total of 109 patients (23.8%) were diagnosed with possible or probable CAA. CAA prevalence was highest in aMCI (39.4%) and MD (28.4%). Of patients with possible or probable CAA, 30.3% were under platelet aggregation inhibition, 12.8% were treated with novel oral anticoagulants and 3.7% received phenprocoumon treatment. Regarding the whole study cohort, patients under oral anticoagulation showed more cerebral microbleeds (p = 0.047). There was no relationship between oral anticoagulation therapy and the frequency of cortical superficial siderosis (p = 0.634). CONCLUSION: CAA is a frequent phenomenon in older patients with cognitive disorders. Almost half of CAA patients receive anticoagulant therapy. Oral anticoagulation is associated with a higher number of cortical and subcortical microbleeds.

Cortical superficial siderosis is associated with reactive astrogliosis in cerebral amyloid angiopathy.

BACKGROUND: Cortical superficial siderosis (cSS) has recently emerged as one of the most important predictors of symptomatic intracerebral hemorrhage and is a risk factor for post-stroke dementia in cerebral amyloid angiopathy (CAA). However, it remains unknown whether cSS is just a marker of severe CAA pathology or may itself contribute to intracerebral hemorrhage risk and cognitive decline. cSS is a chronic manifestation of convexal subarachnoid hemorrhage and is neuropathologically characterized by iron deposits in the superficial cortical layers. We hypothesized that these iron deposits lead to local neuroinflammation, a potentially contributory pathway towards secondary tissue injury. METHODS: Accordingly, we assessed the distribution of inflammatory markers in relation to cortical iron deposits in post-mortem tissue from CAA cases. Serial sections from the frontal, parietal, temporal, and occipital lobes of nineteen autopsy cases with CAA were stained with Perls' Prussian blue (iron) and underwent immunohistochemistry against glial fibrillary acidic protein (GFAP, reactive astrocytes) and cluster of differentiation 68 (CD68, activated microglia/macrophages). Digitized sections were uploaded to the cloud-based Aiforia® platform, where deep-learning algorithms were utilized to detect tissue, iron deposits, and GFAP-positive and CD68-positive cells. RESULTS: We observed a strong local relationship between cortical iron deposits and reactive astrocytes. Like cSS-related iron, reactive astrocytes were mainly found in the most superficial layers of the cortex. Although we observed iron within both astrocytes and activated microglia/macrophages on co-stains, there was no clear local relationship between the density of microglia/macrophages and the density of iron deposits. CONCLUSION: Iron deposition resulting from cSS is associated with local reactive astrogliosis.

The Acute Superficial Siderosis Syndrome - Clinical Entity, Imaging Findings, and Histopathology.

Superficial siderosis is a consequence of repetitive bleeding into the subarachnoid space, leading to toxic iron and hemosiderin deposits on the surface of the brain and spine. The clinical and radiological phenotypes of superficial siderosis are known to manifest over long time intervals. In contrast, this study defines the "acute superficial siderosis syndrome" and illustrates typical imaging and histopathological findings of this entity. We describe the case of a 61-year-old male patient who was diagnosed with a melanoma metastasis in the right frontal cortex in February 2019. Within a few weeks he developed a progressive syndrome characterized by cerebellar ataxia, gait disturbance, signs of myelopathy, and radiculopathy. MRI revealed ongoing hemorrhage from the metastasis into the lateral ventricle and the subarachnoid space. A semiquantitative assessment of three subsequent MRI within an 8-week period documented the rapid development of superficial siderosis along the surface of the cerebellum, the brain stem, and the lower parts of the supratentorial regions on T2*-weighted sequences. The diagnosis of a superficial siderosis was histopathologically confirmed by identifying iron and hemosiderin deposits on the cortex along with astrogliosis. The recognition of this "acute superficial siderosis syndrome" triggered surgical removal of the hemorrhagic metastasis. Based on a single case presentation, we define the "acute superficial siderosis syndrome" as a clinical entity and describe the radiological and histopathological characteristics of this entity. Early recognition of this syndrome may allow timely elimination of the bleeding source, in order to prevent further clinical deterioration.

Epilepsy in cerebral amyloid angiopathy: an observational retrospective study of a large population.

OBJECTIVE: Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous intracranial hemorrhage in older adults. Epilepsy represents a possible sequela of the disease. To date, studies on epilepsy in CAA are lacking, and the few data available mainly focus on CAA-related inflammation (CAA-ri), the inflammatory form of the disease. METHODS: In this retrospective observational study, we consecutively recruited CAA patients observed over a time span of 10 years, collecting demographic, clinical, and instrumental data. Significant baseline characteristics were evaluated as potential risk factors for the development of epilepsy in the CAA population, and in the subgroups of CAA-ri and CAA without inflammatory reaction (CAA-nri). The effect of potential risk factors for epilepsy was measured as odds ratio with 95% confidence interval. RESULTS: Within 96 recruited CAA cases, 33 (34.4%) developed epilepsy during follow-up (median = 13.5 months). The prevalent type of seizure was focal (81.3%); 12.1% of the epileptic patients presented status epilepticus, and 6.1% developed drug-resistant epilepsy. Electroencephalographic traces revealed slow and epileptic discharge activity in the majority of epileptic patients, but also in those without epilepsy. The presence of focal or disseminated cortical superficial siderosis (cSS) was associated with an increased risk of epilepsy in the CAA-nri group, and the association with CAA-ri and epilepsy was present in the overall population. SIGNIFICANCE: Epilepsy is a common manifestation during the course of CAA, where CAA-ri and cSS represent predisposing factors for the development of seizures. These data suggest the importance of a deep characterization of CAA patients, to better select those more prone to develop epilepsy.

Cerebrospinal fluid biomarkers of superficial siderosis in patients with spontaneous intracranial hypotension.

BACKGROUND AND PURPOSE: Spontaneous intracranial hypotension (SIH) is an important etiology of infratentorial superficial siderosis (iSS) of the central nervous system. However, the prevalence of iSS amongst patients with SIH is unknown and the imaging findings of iSS might represent a late stage of disease. The aim was to identify cerebrospinal fluid (CSF) biomarkers of iSS in patients with SIH. METHODS: Consecutive patients evaluated for SIH at our institution between May 2017 and January 2019 were included. Lumbar CSF samples were analyzed for the presence of ferritin and bilirubin. Magnetic resonance imaging was assessed for the presence of iSS. RESULTS: Twenty-four patients with SIH were included. CSF samples were positive for bilirubin in 2/19 (10.5%). CSF ferritin was elevated in 7/23 (30.4%). Signs of iSS on imaging were present in four patients (16.7%). All patients with imaging signs of iSS demonstrated elevated CSF ferritin. Ferritin level was significantly higher amongst patients demonstrating iSS compared to those without (median 45.0 vs. 11.0 µg/l; p = 0.003). Symptom duration was longer in patients with iSS than in patients without iSS (median 40 months vs. 9 months, p = 0.018). CONCLUSION: Cerebrospinal fluid alterations indicative of iSS are prevalent amongst patients with SIH. It is speculated that a preclinical phase without symptoms or imaging signs but during which elevated biomarkers of the disease are apparent from CSF analysis might exist. It is suggested that measurement of CSF ferritin is incorporated in the work-up of patients with SIH to identify those at risk of developing iSS.

Incidence and risk factors associated with seizures in cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is a common cause of intracranial hemorrhage (ICH), which is a risk factor for seizures. The incidence and risk factors of seizures associated with a heterogeneous cohort of CAA patients have not been studied. METHODS: We conducted a retrospective study of patients with CAA treated at Mayo Clinic Florida between 1 January 2015 and 1 January 2021. CAA was defined using the modified Boston criteria version 2.0. We analyzed electrophysiological and clinical features, and comorbidities including lobar ICH, nontraumatic cortical/convexity subarachnoid hemorrhage (cSAH), superficial siderosis, and inflammation (CAA with inflammation [CAA-ri]). Cognition and mortality were secondary outcomes. Univariate and multivariate analyses were performed to determine risk of seizures relative to clinical presentation. RESULTS: Two hundred eighty-four patients with CAA were identified, with median follow-up of 35.7 months (interquartile range = 13.5-61.3 months). Fifty-six patients (19.7%) had seizures; in 21 (37.5%) patients, seizures were the index feature leading to CAA diagnosis. Seizures were more frequent in females (p = 0.032) and patients with lobar ICH (p = 0.002), cSAH (p = 0.030), superficial siderosis (p < 0.001), and CAA-ri (p = 0.005), and less common in patients with microhemorrhage (p = 0.006). After controlling for age and sex, lobar ICH (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.1-4.2), CAA-ri (OR = 3.8, 95% CI = 1.4-10.3), and superficial siderosis (OR = 3.7, 95% CI = 1.9-7.0) were independently associated with higher odds of incident seizures. CONCLUSIONS: Seizures are common in patients with CAA and are independently associated with lobar ICH, CAA-ri, and superficial siderosis. Our results may be applied to optimize clinical monitoring and management for patients with CAA.

Cerebellar Superficial Siderosis in Cerebral Amyloid Angiopathy on 1.5T T2*-Weighted Imaging.

BACKGROUND: Cerebellar superficial siderosis (SS) has been recently reported to be present in about 10% of both hereditary and sporadic cerebral amyloid angiopathy (CAA) on 3T MRI using primarily susceptibility-weighted imaging. OBJECTIVES: Our aim was to assess cerebellar SS in sporadic CAA patients using 1.5T T2*-weighted MRI and to evaluate possible underlying mechanisms. METHOD: We retrospectively screened MRI scans of sporadic probable CAA patients initially presenting with intracerebral hemorrhage-, acute subarachnoid hemorrhage- or cortical SS-related symptoms between September 2009 and January 2022 registered in our stroke database. Patients with familial CAA were excluded. On 1.5T T2*-weighted MRI, cerebellar SS (including kappa statistics for interobserver agreement) was assessed together with typical CAA hemorrhagic features and with the presence of supratentorial macrobleed and cortical SS adjacent to the tentorium cerebelli (TC) and TC hemosiderosis. RESULTS: We screened 151 patients and finally included 111 CAA patients (median age 77) with cerebellar SS observed in 6 (5%) patients. Cerebellar SS presence was associated with a higher number of supratentorial macrobleeds (median n = 3 vs. n = 1, p = 0.0012), presence of supratentorial macrobleed adjacent to the TC (p = 0.002), and TC hemosiderosis (p = 0.005). CONCLUSIONS: Cerebellar SS in CAA patients can be identified on 1.5T T2*-weighted imaging. Associated MRI characteristics suggest contamination from supratentorial macrobleeds.

Anterior horn damage in brachial multisegmental amyotrophy with superficial siderosis and dural tear: an autopsy case report.

BACKGROUND: Patients with superficial siderosis (SS) rarely show brachial multisegmental amyotrophy with ventral intraspinal fluid collection accompanied with dural tear. CASE PRESENTATION: We describe spinal cord pathology of a 58-year-old man who developed brachial multisegmental amyotrophy with ventral intraspinal fluid collection from the cervical to lumbar spinal levels accompanied with SS, dural tear, and snake-eyes appearance on magnetic resonance imaging (MRI). Radiological and pathological analyses detected diffuse and prominent superficial deposition of hemosiderin in the central nervous system. Snake-eyes appearance on MRI expanded from the C3 to C7 spinal levels without apparent cervical canal stenosis. Pathologically, severe neuronal loss at both anterior horns and intermediate zone was expanded from the upper cervical (C3) to middle thoracic (Th5) spinal gray matter, and these findings were similar to compressive myelopathy. CONCLUSION: Extensive damage of the anterior horns in our patient may be due to dynamic compression induced by ventral intraspinal fluid collection.

Preceding symptoms and temporal development of cortical superficial siderosis in cerebral amyloid angiopathy: a case report.

BACKGROUND: We present a case illustrating evolution of symptoms and brain magnetic resonance imaging in cortical superficial siderosis. CASE PRESENTATION: A 74-year-old man with no prior medical history presented with transient focal neurological episodes with subtle imaging changes. There was no evidence of cortical superficial siderosis. Two weeks later, the patient was readmitted with new episodes, and had developed cortical superficial siderosis adjacent to a cerebral microbleed. Transient focal neurological episode secondary to cortical superficial siderosis was diagnosed together with probable cerebral amyloid angiopathy. CONCLUSION: Clinical symptoms may precede the development of cortical superficial siderosis prior to being detectable on brain MRI. This case highlights the temporal development of cortical superficial siderosis.