Contribution of convexal subarachnoid hemorrhage to disease progression in cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy-related cortical superficial siderosis (cSS) seems to indicate an increased risk of subsequent intracerebral hemorrhage (ICH). We wanted to identify the mechanisms and sequence of hemorrhagic events which are responsible for this association. METHODS: During a 9-year-period, we identified patients with spontaneous convexal subarachnoid hemorrhage (cSAH) and performed a careful longitudinal analysis of clinical and neuroimaging data. A close imaging-histopathologic correlation was performed in one patient. RESULTS: Of 38 cSAH patients (mean age, 77±11 years), 29 (76%) had imaging features of cerebral amyloid angiopathy on baseline magnetic resonance imaging. Twenty-six (68%) had cSS. Sixteen subjects underwent postcontrast magnetic resonance imaging. Extravasation of gadolinium at the site of the acute cSAH was seen on all postcontrast scans. After a mean of 24±22 (range 1-78) months of follow-up, 15 (39%) had experienced recurrent cSAHs and 14 (37%) had suffered lobar ICHs. Of 22 new ICHs, 17 occurred at sites of previous cSAHs or cSS. Repeated neuroimaging showed expansion of cSAH into the brain parenchyma and evolution of a lobar ICH in 4 patients. Propagation of cSS was observed in 21 (55%) patients, with 14 of those having experienced recurrent cSAHs. In the autopsy case, leakage of meningeal vessels affected by cerebral amyloid angiopathy was noted. CONCLUSIONS: In cerebral amyloid angiopathy, leakage of meningeal vessels seems to be a major cause for recurrent intrasulcal bleedings, which lead to the propagation of cSS and indicate sites with increased vulnerability for future ICH. Intracerebral bleedings may also develop directly from or in extension of a cSAH.

Cortical Superficial Siderosis and Risk of Bleeding after Thrombolysis for Ischemic Stroke.

BACKGROUND: Cortical superficial siderosis (CSS) is a neuroimaging marker of cerebral amyloid angiopathy and has been associated with a high risk for early subsequent major intracranial hemorrhage (ICH). Therefore, many experts recommend withholding of antithrombotic medication to patients with CSS. In this study, we sought to investigate the prevalence of CSS and the associated risk of ICH in the setting of intravenous thrombolysis (IVT) for ischemic stroke. METHODS: We retrospectively searched the medical documentation system of our primary and tertiary care university clinic for all patients with ischemic stroke that received IVT from 2009 to December 2014. All available imaging data were reviewed in a standardized manner and blinded to any clinical data for the presence of CSS and ICH. CSS was defined as linear signal loss along the cerebral cortex on gradient echo T2*-weighted sequences. A stroke neurologist, who was blinded to the neuroimaging data, extracted the corresponding clinical data including follow-up information. RESULTS: We identified 298 patients that received IVT and had undergone brain MRI (mean age 67.6 ± 12.6 years, 59.4% male). Cerebral MRI was performed in 116 patients (38.9%) before and in 182 patients (61.1%) after IVT (median time from stroke symptom onset to MRI: 1 day; range 0-7 days). Only 3 patients (2 females and 1 male aged 90, 76 and 73 years, respectively) had CSS (1%). All of them had a middle cerebral artery (MCA) stroke with a corresponding vessel occlusion. The 76-year-old female patient had extensive CSS and numerous cerebral microbleeds and received another IVT treatment for recurrent MCA stroke 8 months after the first event. After both IVTs, she had clinically asymptomatic small ICH outside the ischemic infarct and distant from CSS. The 2 other patients had only mild to moderate CSS and did not experience any ICH on postthrombolytic imaging. CONCLUSIONS: The prevalence of CSS in a clinical cohort of stroke patients that received IVT was low and thus does not appear to pose a substantial risk for symptomatic ICH although this may occur in individual patients. However, such analysis also needs to be extended to the very old stroke patients in whom IVT is increasingly used.

Sex-related differences of acute stroke unit care: results from the Austrian stroke unit registry.

BACKGROUND AND PURPOSE: Sex-related differences in quality of acute stroke care are an important concern with limited data available, specifically regarding stroke unit (SU) setting. We used the prospective nationwide Austrian SU registry to address this issue. METHODS: Our analysis covered an 8-year time period (January 2005 to December 2012) during which all patients with transient ischemic attack or ischemic stroke admitted to 1 of 35 Austrian SU had been captured in the registry. These data were analyzed for age-adjusted preclinical and clinical characteristics and quality of acute stroke care in men and women. In addition, we assessed the outcome at 3 months in multivariate analysis. RESULTS: A total of 47 209 individuals (47% women) had received SU care. Women were significantly older (median age: 77.9 versus 70.3 years), had higher pre-existing disability and more severe strokes. Correcting for age, no significant sex-related differences in quality of care were identified with comparable onset-to-door times, times to and rates of neuroimaging, as well as door-to-needle times and rates of intravenous thrombolysis (14.5% for both sexes). Despite equal acute stroke care and a comparable rate of neurorehabilitation, women had a worse functional outcome at 3-month follow-up (modified Rankin scale 3-5: odds ratio, 1.26; 95% confidence interval [1.17-1.36]), but a lower mortality (odds ratio, 0.70; 95% confidence interval [0.78-0.88]) after correcting for confounders. CONCLUSIONS: We identified no disproportions in quality of care in the acute SU setting between men and women, but the outcome was significantly different. Further studies on the poststroke period including socioeconomic aspects are needed to clarify this finding.

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis.

OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31). CONCLUSIONS: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.

Clinical presentation, etiology, and long-term prognosis in patients with nontraumatic convexal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Nontraumatic subarachnoid hemorrhage at the convexity of the brain (cSAH) is an incompletely characterized subtype of nonaneurysmal subarachnoid bleeding. This study sought to systematically describe the clinical presentation, etiology, and long-term outcome in patients with cSAH. METHODS: For a 6-year period, we searched our radiological database for patients with nontraumatic nonaneurysmal subarachnoid hemorrhages (n=131) seen on CT or MRI. By subsequent image review, we identified 24 patients with cSAH defined by intrasulcal bleeding restricted to the hemispheric convexities. We reviewed their medical records, analyzed the neuroimaging studies, and followed up patients by telephone or a clinical visit. RESULTS: The 24 patients with cSAH had a mean age of 70 years (range, 37-88 years), 20 (83%) were >60 years, and 13 (54%) were women. Patients often presented with transient sensory and/or motor symptoms (n=10 [42%]) and seizures (n=5 [21%]), whereas headaches typical of subarachnoid hemorrhage were rare (n=4 [17%]). MRI provided evidence for prior bleedings in 11 patients (microbleeds in 10 and parenchymal bleeds in 5) with a bleeding pattern suggestive of cerebral amyloid angiopathy in 5 subjects. At follow-up (after a mean of 33 months), 14 patients (64%) had an unfavorable outcome (modified Rankin scale score 3-6), including 5 deaths. We did not observe recurrent cSAH. CONCLUSIONS: Our data suggest that cSAH often presents with features not typical for subarachnoid bleeding. In the elderly, cSAH is frequently associated with bleeding-prone conditions such as cerebral amyloid angiopathy. Recurrence of cSAH is rare but the condition itself is a marker of poor prognosis.

Acute and Chronic Kidney Dysfunction and Outcome After Stroke Thrombectomy.

Data on the impact of kidney dysfunction on outcome in patients with stroke due to large vessel occlusion are scarce. The few available studies are limited by only considering single kidney parameters measured at one time point. We thus investigated the influence of both chronic kidney disease (CKD) and acute kidney injury (AKI) on outcome after mechanical thrombectomy. We included consecutive patients with anterior circulation large vessel occlusion stroke receiving mechanical thrombectomy at our center over an 8-year period. We extracted clinical data from a prospective registry and investigated kidney serum parameters at admission, the following day and throughout hospital stay. CKD and AKI were defined according to established nephrological criteria. Unfavorable outcome was defined as scores of 3-6 on the modified Rankin Scale 3 months post-stroke. Among 465 patients, 31.8% had an impaired estimated glomerular filtration rate (eGFR) at admission (< 60 ml/min/1.73 m2). Impaired admission eGFR was related to unfavorable outcome in univariable analysis (p = 0.003), but not after multivariable adjustment (p = 0.96). Patients frequently met AKI criteria at admission (24.5%), which was associated with unfavorable outcome in a multivariable model (OR 3.03, 95% CI 1.73-5.30, p < 0.001). Moreover, patients who developed AKI during hospital stay also had a worse outcome (p = 0.002 in multivariable analysis). While CKD was not associated with 3-month outcome, we identified AKI either at admission or throughout the hospital stay as an independent predictor of unfavorable prognosis in this study cohort. This finding warrants further investigation of kidney-brain crosstalk in the setting of acute stroke.

Acute diffusion-weighted imaging lesions in cerebral amyloid angiopathy-related convexal subarachnoid hemorrhage.

Small acute diffusion-weighted imaging (DWI) lesions can accompany intracerebral hemorrhage due to cerebral amyloid angiopathy (CAA). We therefore examined the occurrence of such lesions in the context of CAA-related convexal subarachnoid hemorrhage (cSAH) both in a cross-sectional and longitudinal manner. DWI lesions were noted in 14/29 (48%) patients at their index cSAH and 12/21 patients (57%) showed acute small DWI lesions at follow-up MRI. Forty-four of 71 (62%) DWI lesions were spatially related to areas of cortical superficial siderosis. Clarification of the implications of our finding needs the investigation of larger patient groups.

Autonomic dysfunction and hemodynamics in vitamin B12 deficiency.

Orthostatic hypotension in patients with cobalamin (Cbl) deficiency has been reported previously in isolated cases but we are not aware of detailed systematic studies of hemodynamic and autonomic nervous system function in patients with cobalamin deficiency. We investigated hemodynamic and autonomic responses to 60 degrees passive head up tilt (HUT) in 21 patients with vitamin B12 deficiency, 21 healthy age-matched control subjects and 9 age-matched patients with diabetes mellitus (DM) and established diabetic neuropathy. To systematically assess hemodynamic and autonomic nervous system function, we performed measurements of heart rate, beat-to-beat systolic and diastolic blood pressure, stroke index, cardiac index, total peripheral resistance index, total power, low (LF) and high (HF) frequency oscillatory component of heart rate variability, LF/HF ratio and spontaneous baroreflex sensitivity. As compared to controls, we found a significant fall of systolic blood pressure during 60 consecutive beats directly after head up tilt; furthermore, a significantly blunted fall of stroke index, cardiac index and a lack of increase of total peripheral resistance index for the duration of tilt in patients with diabetes mellitus and in patients with vitamin B12 deficiency. As compared to controls, we observed an altered response of spectral indices of sympathetic activation and vagal withdrawal and an impaired modulation of baroreflex sensitivity during head up tilt suggestive of a complex modification in the neural control activities in patients with cobalamin deficiency, which was comparable to that observed in patients with diabetes mellitus and established autonomic neuropathy. The results suggest that vitamin B12 deficiency causes autonomic dysfunction with similar hemodynamic consequences and patterns of autonomic failure as seen in diabetic autonomic neuropathy. Defective sympathetic activation may be the cause for orthostatic hypotension, which is occasionally seen in patients with vitamin B12 deficiency. It is concluded that patients with orthostatic hypotension should be screened for cobalamin deficiency.

Cerebrovascular complications and granuloma formation after wrapping or coating of intracranial aneurysms with cotton gauze and human fibrin adhesives: results from a single-center patient series over a 5-year period.

OBJECT: Reinforcement of intracranial aneurysms (IAs) by wrapping or coating is a well-established therapeutic approach to those IAs not amenable to any other definitive treatment, but has been associated with complications such as parent artery narrowing, granuloma formation, and ischemic stroke. The goal of this study was to systematically investigate cerebrovascular complications following this procedure. METHODS: The authors' hospital database was searched for all patients who underwent wrapping or coating of IAs with cotton gauze and human fibrin adhesives between October 2006 and October 2011. The follow-up records of these patients were extracted, including regular clinical visits and vascular imaging. RESULTS: Five hundred sixty-seven patients were treated for IAs over the 5-year period: 303 patients underwent endovascular strategies and 264 underwent craniotomies. Wrapping or coating of IAs was performed in 20 patients (3.5%). Parent artery narrowing occurred in 5 (25%) of the 20 patients and was associated with major ischemic strokes in 4 patients and severe headache in another. Ischemic strokes were associated with parent artery narrowing, which occurred early postoperatively in 2 patients or was a consequence of granuloma formation in 2 patients 1 and 2 months after the procedure, respectively. CONCLUSIONS: These data should add to the awareness of significant cerebrovascular complications following wrapping or coating of IAs with cotton gauze and human fibrin adhesives and indicate that major ischemic strokes need to be included in the risk/benefit considerations during decision making for such treatment strategies. Patients who receive IA wrapping should be monitored and followed up closely for arterial narrowing and granuloma formation.

Multimodality MRI and MRA for decision making in minor stroke: a case with internal carotid and distal middle cerebral artery occlusion.

We report the case of a 65-year-old man who presented with mild, rapidly improving stroke symptoms. Acute magnetic resonance imaging disclosed no diffusion abnormalities but a tandem internal carotid artery/distal middle cerebral artery occlusion associated with a large corresponding deficit on perfusion imaging. In addition, there was a cross-flow to the middle cerebral artery via the anterior communicating artery. Therefore, intravenous thrombolysis was initiated that led to rapid reopening of the middle cerebral artery and left the patient free of symptoms. Our observation highlights the possible benefit of systemic thrombolytic treatment even in the setting of an internal carotid artery occlusion and the substantial contribution of multimodal magnetic resonance imaging for a risk-benefit estimate.

Community acquired Staphylococcus aureus meningitis and cerebral abscesses in a patient with a hyper-IgE and a Dubowitz-like syndrome.

The Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency which recently has been associated with heterozygous dominant-negative mutations in the signal transducer and activator of transcription 3 (STAT3). Although HIES is characterized by recurrent staphylococcal infections, the microbial invasion of the central nervous system (CNS) is definitively uncommon. We here report on Staphylococcus aureus meningitis and cerebral abscesses acquired in the community in a 31-year-old female patient with a de novo heterozygous mutation of STAT3 and a Dubowitz-like syndrome characterized by growth retardation, microcephaly and eczema. The patient presented with a relative paucity of clinical symptoms despite severe cerebrospinal fluid pathology and multiple cerebral abscesses. Antimicrobial as well as treatment with intravenous immunoglobulin was well tolerated and led to a slow recovery over a 6 months period. Our observation adds community acquired S. aureus meningitis to the list of life-threatening infections in STAT3-deficient HIES and should also raise awareness for the unusual clinical presentation of severe neuroinfection in this syndrome. Whether the association of HIES with Dubowitz-like syndrome was purely coincidental, possibly supportive of the CNS infection, or suggests a genetic overlap of these syndromes, awaits clarification.

Congenital hearing loss explained in adulthood. Computed tomography of the temporal bone in hemifacial microsomia. A case report.

We present a case of complex hemifacial microsomia (HFM) which was diagnosed at the age of 46 years. Imaging findings of a complex deformity of the temporal bone are presented and connected to a broad range of clinical symptoms. Computed tomography (CT) imaging indications are discussed briefly.