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.

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.

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.

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.

Intraventricular hemorrhage in term infants: a single institutional experience between 2016 and 2020.

PURPOSE: Intraventricular hemorrhage (IVH) of prematurity is a known complication of preterm birth. Intraventricular hemorrhage in term infants is much less commonly encountered. To address the lack of information in the current literature concerning this demographic, we offer demographic and image findings that demonstrate etiology and predict the need for permanent cerebrospinal fluid (CSF) diversion. METHODS: A prospectively maintained database was queried for all patients with intraventricular hemorrhage from 2016 to 2020 treated at our institution. Demographic data and etiology were collected, along with need for and timing of surgical intervention. RESULTS: A total of 150 IVH patients were identified. Of these patients, 138 were excluded due to prematurity. Twelve patients were born at term with IVH. All patients were followed for at least 8 months. Seven patients (58.3%) underwent ventriculoperitoneal (VP) shunt placement, performed between 4 days and 4 months of age. Superficial siderosis detected by MRI during in-patient stay or follow-up showed a sensitivity of 100% and specificity of 60% for the future development of post-hemorrhagic hydrocephalus (PHH) (p < 0.05). All full-term infants who developed PHH (n = 7, 58.3%) obtained a VP shunt. CONCLUSION: IVH in term infants occurs infrequently when compared to IVH of prematurity. Etiology of IVH in term infants remains difficult to ascertain, but the majority of patients did demonstrate risk factors. The presence of superficial siderosis on MRI significantly predicted the development of PHH and eventual need for CSF diversion.

Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects.

PURPOSE: Superficial siderosis, a progressive, debilitating, neurological disease, often presents with bilateral impairment of auditory and vestibular function. We highlight that superficial siderosis is often due to a repairable spinal dural defect of the type that can also cause spontaneous intracranial hypotension. METHODS: Retrospective chart review of five patients presenting with moderate to severe, progressive bilateral sensorineural hearing loss as well as vestibular loss. All patients had developed superficial siderosis from spinal dural defects: three after trauma, one after spinal surgery and one from a thoracic discogenic microspur. RESULTS: The diagnosis was made late in all five patients; despite surgical repair in four, hearing and vestibular loss failed to improve. CONCLUSIONS: In patients presenting with progressive bilateral sensorineural hearing loss, superficial siderosis should be considered as a possible cause. If these patients also have bilateral vestibular loss, cerebellar impairment and anosmia, then the diagnosis is likely and the inevitable disease progress might be halted by finding and repairing the spinal dural defect.

A case of aneurysmal subarchnoid haemorrhage and superficial siderosis complicated by prospagnosia, simultagnosia and alexia without agraphia.

A 42-year-old lady presented with acute aneurysmal subarachnoid haemorrhage and developed difficulty recognising faces (prosopagnosia), inability to process visual information in busy environments (simultagnosia) and difficulty to read (alexia). She was subsequently found to have superficial siderosis on MRI.

SWI versus GRE-T2*: Assessing cortical superficial siderosis in advanced cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cortical superficial siderosis (cSS) is a key neuroimaging marker of cerebral amyloid angiopathy (CAA) detected on blood-sensitive magnetic resonance imaging (MRI). We aimed to assess cSS in advanced CAA patients and explore differences in its evaluation between susceptibility weighted imaging (SWI) and gradient recalled echo-T2* (GRE-T2*). MATERIALS AND METHODS: Neuroimaging data gathered from a prospective cohort of CAA patients with probable or definite CAA were retrospectively analyzed by two independent raters. SWI and GRE-T2* were used to assess presence and severity (absent, focal [≤3 sulci] or disseminated [>3 sulci]) of cSS and number of foci. Ratings were compared between sequences and inter-rater agreement was determined. Post hoc analysis explored differences in cSS multifocality scores. RESULTS: We detected cSS in 38 patients with SWI and in 36 with GRE-T2* (70.4% versus 66.7%; P=0.5). The two raters agreed in detecting more disseminated cSS when using SWI: 16 focal (29.63%) and 20 disseminated (37.04%) cases of cSS seen on GRE-T2* and 11 (20.37%) focal and 27 (50%) disseminated cSS cases seen using SWI (P=0.008). Inter-rater agreement was equivalent for the two sequences (κpresence 0.7 versus 0.69; κseverity 0.74 versus 0.66) for assessing both presence and severity of cSS. Post hoc analysis showed higher multifocality scores from both raters' SWI evaluations, with agreement equivalent to that for T2* evaluations. CONCLUSIONS: Our findings suggest that SWI ratings could show more disseminated cSS and higher multifocality scores in advanced CAA patients with inter-rater reliability equivalent to that obtained using GRE-T2*, regardless of level of experience.

Spinal dural leaks in patients with infratentorial superficial siderosis of the central nervous system-Refinement of a diagnostic algorithm.

BACKGROUND AND PURPOSE: Superficial siderosis of the central nervous system is a sporadic finding in magnetic resonance imaging, resulting from recurrent bleedings into the subarachnoid space. This study aimed to determine the frequency of spinal dural cerebrospinal fluid (CSF) leaks amongst patients with a symmetric infratentorial siderosis pattern. METHODS: In all, 97,733 magnetic resonance images performed between 2007 and 2018 in our neurocenter were screened by a keyword search for "hemosiderosis" and "superficial siderosis." Siderosis patterns on brain imaging were classified according to a previously published algorithm. Potential causative intracranial bleeding events were also assessed. Patients with a symmetric infratentorial siderosis pattern but without causative intracranial bleeding events in history were prospectively evaluated for spinal pathologies. RESULTS: Forty-two patients with isolated supratentorial siderosis, 30 with symmetric infratentorial siderosis and 21 with limited (non-symmetric) infratentorial siderosis were identified. Amyloid angiopathy and subarachnoid hemorrhage were causes for isolated supratentorial siderosis. In all four patients with a symmetric infratentorial siderosis pattern but without a causative intracranial bleeding event in history, spinal dural abnormalities were detected. Dural leaks were searched for in patients with symmetric infratentorial siderosis and a history of intracranial bleeding event without known bleeding etiology, considering that spinal dural CSF leaks themselves may also cause intracranial hemorrhage, for example by inducing venous thrombosis due to low CSF pressure. Thereby, one additional spinal dural leak was detected. CONCLUSIONS: Persisting spinal dural CSF leaks can frequently be identified in patients with a symmetric infratentorial siderosis pattern. Diagnostic workup in these cases should include magnetic resonance imaging of the whole spine.

Targeted detection and repair of a spinal dural defect associated with successful biochemical resolution of subarachnoid bleeding in classical infratentorial superficial siderosis.

BACKGROUND AND IMPORTANCE  : Classical infratentorial superficial siderosis (iSS) is characterised by repeated insidious bleeding into the subarachnoid space, leading to haemosiderin deposition within the subpial layers of the brainstem, cerebellum and spinal cord, sometimes with supratentorial involvement. Although nearly always associated with a dural defect (usually from previous trauma or neurosurgery) there is little evidence to support definitive investigation and management strategies. Here, we present a novel investigation strategy to identify a dural defect and subsequent successful surgical repair with biochemical resolution of subarachnoid bleeding. CLINICAL PRESENTATION: A 55-year-old gentleman presented with a 15-year progressive history of sensorineural deafness, followed by a slowly worsening gait ataxia. He had previously sustained cranio-spinal trauma. On examination there were features of myelopathy and ataxia. MRI demonstrated classical iSS, affecting cerebellum and cerebral cortices, with a cervicothoracic epidural CSF collection. Lumbar puncture (LP) revealed elevated ferritin 413 ng/mL and red cell count of 4160. Reverse CT myelography, a novel technique involving contrast injection into the collection, delineated a dural defect at the T9/T10 level that was not present on conventional myelography. Following surgical repair, repeat LP twelve months later demonstrated biochemical improvement (ferritin 18 ng/mL, red cells < 1). There was no further neurological deterioration in symptoms during eighteen months follow-up. CONCLUSION: We show the value of a rational targeted investigation pathway in identifying a surgically reparable dural defect underlying classical iSS. We also provide proof of concept that surgical repair can facilitate biochemical resolution of subarachnoid bleeding and might prevent progression of neurological disability.