Practical uses of the BENCHMARK™ BMX®81 in the road less travelled: Guide catheter comparison for radial access in neurovascular intervention.

BACKGROUND: Radial arterial access has gained interest for neurovascular procedures in recent years. Although there are no randomized control trials for neurointervention procedures using radial access, there is growing literature demonstrating its feasibility and favorable outcomes. Equipment technical improvements, like the recently introduced BENCHMARK™ BMX®81 System, have made radial navigation safer, with improved maneuverability and support for a variety of procedures. We present a multicenter case series highlighting our institutional radial access experience comparing the BMX®81 with alternative catheters. METHODS: Multicenter retrospective cohort study of 80 patients who underwent neurovascular procedures through a radial approach. In half of the cases a BENCHMARK™ BMX®81 System was used. The comparison group consisted of the BENCHMARK™071 and 96, Neuron MAX®088 and BALLAST™ systems. Procedures included endovascular thrombectomy, carotid and brachiocephalic artery stenting, middle meningeal artery embolization, flow diverter stenting, vertebral artery sacrifice, aneurysm coiling, and WEB™ device deployment. RESULTS: In our series, the BMX®81 was successful in the navigation of the anatomy to the target location in 95% of cases. No radial access or BMX®81 related complications were identified. There was no significant difference in fluoroscopy time between the BMX81 and the comparison group. Four patients in the comparison group had catheter-related complications due to vasospasm. Eighty-six percent of BMX®81 cases had satisfactory outcomes and no technical difficulties. The remainder presented technical difficulties, but none of these were considered secondary to the puncture site or support structure. CONCLUSIONS: The BENCHMARK™ BMX®81 System is a recently developed guiding catheter which has design and size features supporting radial access for a variety of neurovascular interventions. Early multicenter experience highlights the ease of use and versatility of this new catheter as an alternative to transfemoral access as well as other catheters used for radial access.

ASPECTS estimation using dual-energy CTA-derived virtual non-contrast in large vessel occlusion acute ischemic stroke: a dose reduction opportunity for patients undergoing repeat CT?

PURPOSE: Recent studies have shown the feasibility of dual-energy CT (DECT) virtual non-contrast (VNC) for determining infarct extent. In this study, patients presenting with large-vessel occlusion (LVO) acute ischemic stroke (AIS), we assess whether ASPECTS on DECTA-VNC differs from non-contrast CT (NCCT). METHODS: After IRB approval, LVO-AIS patients undergoing NCCT and DECTA between October 2016 and September 2018 were retrospectively reviewed. DECTA-VNC images were derived using Syngo.via (Siemens, Erlangen, Germany). ASPECTS was scored by two blinded neuroradiologists. Square-weighted kappa statistic, diagnostic performance, Wilcoxon signed-rank tests between groups, and CT doses were calculated. RESULTS: Fifty-one patients met inclusion criteria, with median age of 76 (IQR 67-82); 26/51 (51%) were female. Median time between last-known-well and CT was 120 min (IQR 60-252). DECTA-VNC ASPECTS score differed by ≤ 1 from consensus NCCT in 49/51 (96%) patients for reader 1 and in 46/51 (90%) for reader 2. ASPECTS on DECTA-SI and consensus NCCT differed by ≤ 1 in 45/51 (88%) for both readers. On a per ASPECTS-region basis, DECTA-VNC had 87% sensitivity, 95% specificity, 0.82% PPV, and 0.96% NPV. ASPECTS inter-rater agreement was highest for DECTA-VNC (κ = 0.71), DECTA-SI (κ = 0.48), and NCCT (κ = 0.40). NCCT median CTDIvol was 63.7 mGy (IQR 60.7-67.2); DLP was 1060.0 mGy·cm (IQR 981.0-1151.5). DECTA-VNC dose was lower: median CTDIvol was 20.9 mGy (IQR 19.8-22.2); DLP was 804.1 (IQR 691.6-869.4), p < 0.0001. CONCLUSION: DECTA-derived VNC yielded similar ASPECTS scores as NCCT and is therefore non-inferior in early ischemia-related low attenuation edema/infarct detection in acute LVO-AIS patients. Further evaluation of the role of DECTA-VNC in AIS imaging is warranted.

A Detailed Analysis of Infarct Patterns and Volumes at 24-hour Noncontrast CT and Diffusion-weighted MRI in Acute Ischemic Stroke Due to Large Vessel Occlusion: Results from the ESCAPE-NA1 Trial.

Background The effect of infarct pattern on functional outcome in acute ischemic stroke is incompletely understood. Purpose To investigate the association of qualitative and quantitative infarct variables at 24-hour follow-up noncontrast CT and diffusion-weighted MRI with 90-day clinical outcome. Materials and Methods The Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke, or ESCAPE-NA1, randomized controlled trial enrolled patients with large-vessel-occlusion stroke undergoing mechanical thrombectomy from March 1, 2017, to August 12, 2019. In this post hoc analysis of the trial, qualitative infarct variables (predominantly gray [vs gray and white] matter involvement, corticospinal tract involvement, infarct structure [scattered vs territorial]) and total infarct volume were assessed at 24-hour follow-up noncontrast CT or diffusion-weighted MRI. White and gray matter infarct volumes were assessed in patients by using follow-up diffusion-weighted MRI. Infarct variables were compared between patients with and those without good outcome, defined as a modified Rankin Scale score of 0-2 at 90 days. The association of infarct variables with good outcome was determined with use of multivariable logistic regression. Separate regression models were used to report effect size estimates with adjustment for total infarct volume. Results Qualitative infarct variables were assessed in 1026 patients (mean age ± standard deviation, 69 years ± 13; 522 men) and quantitative infarct variables were assessed in a subgroup of 358 of 1026 patients (mean age, 67 years ± 13; 190 women). Patients with gray and white matter involvement (odds ratio [OR] after multivariable adjustment, 0.19; 95% CI: 0.14, 0.25; P < .001), corticospinal tract involvement (OR after multivariable adjustment, 0.06; 95% CI: 0.04, 0.10; P < .001), and territorial infarcts (OR after multivariable adjustment, 0.22; 95% CI: 0.14, 0.32; P < .001) were less likely to achieve good outcome, independent of total infarct volume. Conclusion Infarct confinement to the gray matter, corticospinal tract sparing, and scattered infarct structure at 24-hour noncontrast CT and diffusion-weighted MRI were highly predictive of good 90-day clinical outcome, independent of total infarct volume. Clinical trial registration no. NCT02930018 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mossa-Basha in this issue.

Neurosarcoidosis presenting with hypopituitarism.

Hypothalamo-pituitary sarcoidosis is a rare manifestation of sarcoidosis, usually presenting alongside other symptoms of neurosarcoidosis. We describe the case of a 58-year-old man from Ghana who presented with progressive gait disturbance, cognitive dysfunction, hypothermia and bradycardia. He was found to have pituitary stalk thickening on imaging, and lymph node biopsy identified non-caseating granulomatous disease. Serology revealed gonadotropin deficiency, hypothyroidism and central adrenal insufficiency. Treatment with immunomodulatory therapy resulted in resolution of findings on imaging and improved cognition, though pituitary function never recovered. Treatment for his sarcoidosis unfortunately resulted in recurrent infections and avascular necrosis. Work-up, management and ongoing care required multidisciplinary cooperation between the admitting internal medicine team, infectious diseases, respirology, rheumatology, endocrinology and neurology.

Whole-Exome Sequencing in NF1-Related West Syndrome Leads to the Identification of KCNC2 as a Novel Candidate Gene for Epilepsy.

Patients with neurofibromatosis type 1 (NF1) have an increased risk for West syndrome (WS), but the underlying mechanisms linking NF1 and WS are unknown. In contrast to other neurocutaneous syndromes, intracerebral abnormalities explaining the course of infantile spasms (IS) are often absent and the seizure outcome is usually favorable. Several studies have investigated a potential genotype-phenotype correlation between NF1 and seizure susceptibility, but an association was not identified. Therefore, we identified three patients with NF1-related WS (NF1-WS) in a cohort of 51 NF1 patients and performed whole-exome sequencing (WES) to identify genetic modifiers. In two NF1 patients with WS and good seizure outcome, we did not identify variants in epilepsy-related genes. However, in a single patient with NF1-WS and transition to drug-resistant epilepsy, we identified a de novo variant in KCNC2 (c.G499T, p.D167Y) coding for Kv3.2 as a previously undescribed potassium channel to be correlated to epilepsy. Electrophysiological studies of the identified KCNC2 variant demonstrated both a strong loss-of-function effect for the current amplitude and a gain-of-function effect for the channel activation recommending a complex network effect. These results suggest that systematic genetic analysis for potentially secondary genetic etiologies in NF1 patients and severe epilepsy presentations should be done.

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke. METHODS: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018. FINDINGS: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups. INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. FUNDING: Canadian Institutes for Health Research, Alberta Innovates, and NoNO.

Unenhanced Dual-Energy Computed Tomography: Visualization of Brain Edema.

PURPOSE: The aim of this study was to determine whether dual-energy computed tomography (DECT) imaging is superior to conventional noncontrast computed tomography (CT) imaging for the detection of acute ischemic stroke. MATERIALS AND METHODS: This was a retrospective, single-center study of 40 patients who presented to the emergency department (ED) of a major, acute care, teaching center with signs and symptoms of acute stroke. Only those patients who presented to the ED within 4 hours of symptom onset were included in this study. All 40 patients received a noncontrast DECT of the head at the time of presentation. Each patient also received standard noncontrast CT of the head 24 hours after their initial presentation to the ED. "Brain edema" images were then reconstructed using 3-material decomposition with parameters adjusted to suppress gray/white matter contrast while preserving edema and increasing its conspicuity. The initial unenhanced, mixed images, brain edema, and 24-hour follow-up true noncontrast (TNC) images were reviewed and assigned Alberta Stroke Program Early CT scores. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. RESULTS: Of the 40 patients, 28 (70%) were diagnosed with an acute infarction. Brain edema reconstructions were better able to predict end infarction volume, with Alberta Stroke Program Early CT scores similar to the 24-hour follow-up TNC CT (7.75 vs 7.7; P > 0.05), whereas the mixed images routinely underestimated the extent of infarction (8.975 vs 7.7; P < 0.001). Initial TNC images had a sensitivity, specificity, PPV, and NPV of 80% (95% confidence interval [CI], 51.9%-95.7%), 72.7% (95% CI, 39%-94%), 80% (95% CI, 51.9%-95.7%), and 72.73% (95% CI, 51.91%-95.67%), respectively. The DECT brain edema images provided a sensitivity, specificity, PPV, and NPV of 93.33% (95% CI, 68.05%-99.83%), 100% (95% CI, 71.51%-100%), 100% (95% CI, 76.84%-100%), and 91.67% (95% CI, 61.52%-99.79%), respectively. There was very good interrater reliability across all 3 imaging techniques. CONCLUSION: Brain edema reconstructions are able to more accurately detect edema and end-infarct volume as compared with initial TNC images. This provides a better assessment of the degree and extent of infarction and may serve to better guide therapy in the future.

Hypothalamic Inflammation in Human Obesity Is Mediated by Environmental and Genetic Factors.

Obesity is associated with hypothalamic inflammation (HI) in animal models. In the current study, we examined the mediobasal hypothalamus (MBH) of 57 obese human subjects and 54 age- and sex- matched nonobese control subjects by MRI and analyzed the T2 hyperintensity as a measure of HI. Obese subjects exhibited T2 hyperintensity in the left but not the right MBH, which was strongly associated with systemic low-grade inflammation. MRS revealed the number of neurons in the left hypothalamic region to be similar in obese versus control subjects, suggesting functional but not structural impairment due to the inflammatory process. To gain mechanistic insights, we performed nutritional analysis and 16S rDNA microbiome sequencing, which showed that high-fat diet induces reduction of Parasutterella sp. in the gut, which is significantly correlated with MBH T2 hyperintensity. In addition to these environmental factors, we found subjects carrying common polymorphisms in the JNK or the MC4R gene to be more susceptible to HI. Finally, in a subgroup analysis, bariatric surgery had no effect on MBH T2 hyperintensity despite inducing significant weight loss and improvement of peripheral insulin sensitivity. In conclusion, obesity in humans is associated with HI and disturbances in the gut-brain axis, which are influenced by both environmental and genetic factors.

Progressive neurologic dysfunction in a psoriasis patient treated with dimethyl fumarate.

Progressive multifocal leukoencephalopathy (PML) has recently been described in psoriasis or multiple sclerosis patients treated with fumaric acid esters (fumarates), who had developed severe and long-standing lymphocytopenia (<500/mm(3) ). We report a psoriasis patient who presented with progressive neurologic dysfunction and seizures after 2.5 years of fumarate therapy. Despite absolute lymphocyte counts remaining between 500-1000/mm(3) , his CD4(+) and CD8(+) T-cell counts were markedly low. MRI showed right hemispheric and brainstem lesions and JC virus DNA was undetectable in his cerebrospinal fluid. Brain biopsy revealed typical features of PML as well as JC virus-infected neurons. Clinicians should consider PML in the differential diagnosis of fumarate-treated patients presenting with brain lesions or seizures even in the absence of severe lymphocytopenia.

Superselective pseudo-continuous arterial spin labeling angiography.

PURPOSE: To evaluate the utility of a novel non-contrast enhanced, vessel-selective magnetic resonance angiography (MRA) approach based on superselective pseudo-continuous arterial spin labeling (ASL) for the morphologic assessment of intracranial arteries when compared to a clinically used time-of-flight (TOF) MRA. MATERIALS AND METHODS: Three sets of selective ASL angiographies (right and left internal carotid artery, basilar artery) as well as one TOF data set were obtained from each of the five volunteers included in this study on a clinical 1.5T system. The depiction of arterial segments as well as their delineation was evaluated and independently analyzed by two radiologists. Additionally, the ASL angiography approach was performed in two patients suffering from arterio-venous malformations (AVM) in order to illustrate potential applications in a clinical setting. RESULTS: In both angiography techniques, intracranial arteries and their segments (distal branches up to A5 segments of the anterior cerebral arteries, M8 segments of the middle cerebral arteries, and P5 segments of the posterior cerebral arteries) were continuously depicted with excellent inter-reader agreement (κ>0.81). In AVM patients, reconstructed images of the TOF angiography presented similar information about the size and shape of the AVM as did superselective ASL angiography. In addition, the acquired ASL angiograms of selected vessels allowed assessing the blood supply of individually labeled arteries to the AVM which could also be confirmed by digital subtraction angiography. CONCLUSION: Superselective ASL angiography makes it possible to visualize arterial trees of selected vessels, thereby, providing information about the macrovascular blood supply and flow territories of intracranial arteries. Similar image quality is achieved when compared to clinically used TOF angiography with respect to the identification and delineation of arterial segments. Initial application of superselective ASL angiography in two patients with AVM's demonstrates the ability to gather additional important information about feeding vessels and blood supply.

Selective neuronal vulnerability of human hippocampal CA1 neurons: lesion evolution, temporal course, and pattern of hippocampal damage in diffusion-weighted MR imaging.

The CA1 (cornu ammonis) region of hippocampus is selectively vulnerable to a variety of metabolic and cytotoxic insults, which is mirrored in a delayed neuronal death of CA1 neurons. The basis and mechanisms of this regional susceptibility of CA1 neurons are poorly understood, and the correlates in human diseases affecting the hippocampus are not clear. Adopting a translational approach, the lesion evolution, temporal course, pattern of diffusion changes, and damage in hippocampal CA1 in acute neurologic disorders were studied using high-resolution magnetic resonance imaging. In patients with hippocampal ischemia (n=50), limbic encephalitis (n=30), after status epilepticus (n=17), and transient global amnesia (n=53), the CA1 region was selectively affected compared with other CA regions of the hippocampus. CA1 neurons exhibited a maximum decrease of apparent diffusion coefficient (ADC) 48 to 72 hours after the insult, irrespective of the nature of the insult. Hypoxic-ischemic insults led to a significant lower ADC suggesting that the ischemic insult results in a stronger impairment of cellular metabolism. The evolution of diffusion changes show that CA1 diffusion lesions mirror the delayed time course of the pathophysiologic cascade typically observed in animal models. Studying the imaging correlates of hippocampal damage in humans provides valuable insight into the pathophysiology and neurobiology of the hippocampus.

Neurothrombectomy in the treatment of acute ischaemic stroke.

Major ischaemic stroke is a leading cause of morbidity and mortality in industrialized countries. For patients with acute stroke, fast and effective vessel recanalization is important for successful treatment. Neurothrombectomy--that is, angiographically performed mechanical thrombus removal from intracranial arteries--results in higher recanalization rates than with pharmaceutical thrombolysis alone, but the value of this treatment in terms of clinical outcome remains to be established. This article summarizes the history of intra-arterial stroke treatment, outlines the recent developments and the different techniques used, and discusses the results of current studies on neurothrombectomy. Owing to the high morphological and clinical variability of stroke, careful patient selection in future randomized controlled trials will be crucial for assessment of the true potential of neurothrombectomy.

Growth pattern of tumor recurrence following bis-chloroethylnitrosourea (BCNU) wafer implantation in malignant glioma.

Bis-chloroethylnitrosourea (BCNU; Gliadel, Eisai, Tokyo, Japan) is the only therapeutic agent for local chemotherapy of malignant gliomas approved by the US Food and Drug Administration and the European Medicines Agency. In a small patient cohort, it has previously been shown that glioblastomas recur locally despite treatment with BCNU. This raises concern about local treatment with BCNU as a stand-alone measure. The goal of this study was to analyze the growth pattern of tumor recurrence in a larger patient group: 41 patients were included in this study. Tumor recurrences were morphologically categorized as: local, diffuse, distant or multilocular. Thirty-three of the tumors (80%) that recurred were local or diffuse. These results show that BCNU implantation does not provide lasting local tumor control. Our data support the need to incorporate BCNU in to multimodal therapy schemes. The improved survival rates of patients who receive concomitant local and systemic adjuvant treatment support using local therapy to bridge the therapy-free interval of the initial postoperative phase.

Febrile infection-related epilepsy syndrome without detectable autoantibodies and response to immunotherapy: a case series and discussion of epileptogenesis in FIRES.

Febrile infection-related epilepsy syndrome (FIRES) is a severe postinfectious epileptic encephalopathy in previously healthy children and has three phases: the initial phase with a simple febrile infection, a few days later the acute phase characterized by a peracute onset of highly recurrent seizures or refractory status epilepticus often with no more fever and generally without additional neurological features (the classical pure seizure phenotype), and last, the chronic phase with a drug-resistant epilepsy and neuropsychological impairments. FIRES seems to be sporadic and very rare: we estimated the annual incidence in children and adolescents by a prospective hospital-based German-wide surveillance as 1 in 1,000,000. Because of the preceding infection and lacking evidence of infectious encephalitis, an immune-mediated pathomechanism and, therefore, a response to immunotherapies may be involved. To test the hypothesis that antibodies against neuronal structures cause FIRES, we analyzed sera of 12 patients aged 2 to 12 years (median 6 years) and cerebral spinal fluids (CSFs) of 3 of these 12 patients with acute or chronic FIRES. We studied six patients (two including CSF) 1 to 14 weeks (median 3 weeks) and six patients 1 to 6 years (median 3.5 years) after seizure onset. All samples were analyzed for antibodies against glutamate receptors of type N-methyl-D-aspartate (NMDA) and type α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA), gamma-aminobutyric acid (GABA)B-receptors, voltage-gated potassium channel (VGKC)-associated proteins leucin-rich glioma inactivated 1 (LGI1) and contactin-associated protein like 2 (CASPR2), and glutamic acid decarboxylase (GAD) by a multiparametric recombinant immunofluorescence assay employing human embryonic kidney (HEK) cells transfected with cDNAs for the antigens. In addition, indirect immunohistochemistry using rat whole-brain sections was done in three patients. Finally, sera of 10 patients were tested for VGKC complex antibodies by radioimmunoprecipitation assay (RIA). None of the antibody tests were positive in any of the patients. Moreover, steroids, immunoglobulins, and plasmapheresis had no clear effect in the seven patients receiving immunotherapy. The failure of antibody-detection against the known neuronal antigens as well as the ineffectiveness of immunotherapy questions a role for autoantibodies in the epileptogenesis of classical FIRES. As we discuss, other underlying causes need to be considered including the possibility of a mitochondrial encephalopathy.

Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study.

OBJECTIVE: To evaluate the effect of different treatment strategies on enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome. DESIGN: Multicentre retrospective case-control study. SETTING: 23 hospitals in northern Germany. PARTICIPANTS: 298 adults with enterohaemorrhagic E coli induced haemolytic uraemic syndrome. MAIN OUTCOME MEASURES: Dialysis, seizures, mechanical ventilation, abdominal surgery owing to perforation of the bowel or bowel necrosis, and death. RESULTS: 160 of the 298 patients (54%) temporarily required dialysis, with only three needing treatment long term. 37 patients (12%) had seizures, 54 (18%) required mechanical ventilation, and 12 (4%) died. No clear benefit was found from use of plasmapheresis or plasmapheresis with glucocorticoids. 67 of the patients were treated with eculizumab, a monoclonal antibody directed against the complement cascade. No short term benefit was detected that could be attributed to this treatment. 52 patients in one centre that used a strategy of aggressive treatment with combined antibiotics had fewer seizures (2% v 15%, P = 0.03), fewer deaths (0% v 5%, p = 0.029), required no abdominal surgery, and excreted E coli for a shorter duration. CONCLUSIONS: Enterohaemorrhagic E coli induced haemolytic uraemic syndrome is a severe self limiting acute condition. Our findings question the benefit of eculizumab and of plasmapheresis with or without glucocorticoids. Patients with established haemolytic uraemic syndrome seemed to benefit from antibiotic treatment and this should be investigated in a controlled trial.

The entire dural sinus tree is compressed in patients with idiopathic intracranial hypertension: a longitudinal, volumetric magnetic resonance imaging study.

INTRODUCTION: The objective of this study was to explore the volumetric alterations of dural sinuses in patients with idiopathic intracranial hypertension (IIH). METHODS: Standardized cranial magnetic resonance imaging (MRI) was used in 17 patients prior to and following treatment of IIH and in seven controls. Magnetic resonance venographies (MRV) were employed for (a) judgement of circumscript dural sinus stenoses and (b) computation of sinus volumes. Cross-sectional areas (CSA) of the superior sagittal sinuses (SSS) were measured on T2-weighted images. Results of the initial MRIs were compared to those on follow-up MRIs and to results of controls. RESULTS: Stenoses of the transverse sinuses (TS) resulting in cranial venous outflow obstruction (CVOO) were present in 15/17 (88%) patients, normalizing in 7/15 cases (47%) after treatment of IIH. CVOO was not detected in the control group. Segmentation of MRV revealed decreased dural sinus volumes in patients with IIH as compared to controls (P = 0.018). Sinus volumes increased significantly with normalization of intracranial pressure independent from disappearing of TS stenoses (P = 0.007). The CSA of the SSS were normal on the initial MRIs of patients with IIH and increased on follow-up after treatment (P < 0.001). However, volumetries displayed overlap in patients and controls. CONCLUSIONS: Patients with IIH not only exhibit bilateral stenoses of the TS as has been reported, but volume changes of their entire dural sinus system also occur. The potential etiopathological and diagnostic roles of these changes are discussed.

CA1 neurons in the human hippocampus are critical for autobiographical memory, mental time travel, and autonoetic consciousness.

Autobiographical memories in our lives are critically dependent on temporal lobe structures. However, the contribution of CA1 neurons in the human hippocampus to the retrieval of episodic autobiographical memory remains elusive. In patients with a rare acute transient global amnesia, highly focal lesions confined to the CA1 field of the hippocampus can be detected on MRI. We studied the effect of these lesions on autobiographical memory using a detailed autobiographical interview including the remember/know procedure. In 14 of 16 patients, focal lesions in the CA1 sector of the hippocampal cornu ammonis were detected. Autobiographical memory was significantly affected over all time periods, including memory for remote periods. Impairment of episodic memory and autonoetic consciousness exhibited a strong temporal gradient extending 30 to 40 y into the past. These results highlight the distinct and critical role of human hippocampal CA1 neurons in autobiographical memory retrieval and for re-experiencing detailed episodic memories.

Space-occupying cyst development in the resection cavity of malignant gliomas following Gliadel® implantation--incidence, therapeutic strategies, and outcome.

Gliadel® (Eisai Inc., Woodcliff Lake, NJ, USA) is the only therapeutic agent approved by the Food and Drug Administration and the European Medicines Agency for local chemotherapy of malignant gliomas. With increasing use of this treatment, characteristic side effects have become evident. While most side effects can be managed conservatively, cyst formation requires further intervention. From 2004 to 2009 at our institution 88 patients with malignant gliomas were treated with Gliadel®. Ten patients (11%) developed a space-occupying cyst in the resection cavity, seven of which caused clinical symptoms of mass effect that was most prominent 2 weeks after Gliadel® implantation (median=16, range=9-30). Despite dexamethasone treatment symptoms progressed, necessitating various surgical interventions. In four patients the cysts were drained percutaneously through a burrhole using a 19-gauge needle. If puncture was not possible (three patients) or not sufficient (two patients), an Ommaya reservoir was implanted for repetitive drainage. In two patients this treatment was combined with open decompression of the cyst. On average, cysts were drained three times. Eventually the symptoms subsided, corresponding to shrinkage of the cysts as shown on follow-up imaging. We describe a serious side effect of local chemotherapy, which may cause rapid clinical deterioration and require direct intervention. While reservoir implantation apparently represents a more elegant treatment option, our experience shows that draining the cyst, even only a few times, sufficiently ameliorates the symptoms and subsequently reverses and halts further cyst enlargement.