Cerebral oedema is rare in acute-on-chronic liver failure patients presenting with high-grade hepatic encephalopathy.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) has a rapidly progressive disease course associated with significant mortality. The prevalence of clinically significant cerebral oedema in ACLF is unknown. METHODS: We aimed to describe the prevalence of cerebral oedema in a cohort of ACLF adult (>18 years). We identified patients admitted to a single, specialist intensive care unit between January 2005 and January 2011 with high-grade hepatic encephalopathy (≥3) and a clinical picture of either ACLF or chronic liver disease (CLD). Patients who had undergone cranial CT imaging were identified and their imaging reviewed. The ACLF and CLD groups were compared. RESULTS: One thousand and eight patients with CLD were admitted. One hundred and seventy-three patients (110 male) underwent neuroimaging. Eighty-one (48 male) fulfilled criteria for ACLF. Variceal bleeding (30%) and sepsis (31%) were the most frequent precipitants of ACLF. Of those with neuroimaging from the total cohort, 30% of CT scans were normal, 30% demonstrated increased cerebral atrophy for age, 17% small vessel disease and 16% intracranial haemorrhage (ICH). Cerebral oedema was seen in three patients with ACLF only. An increased prevalence of ICH was observed in the ACLF group (23% vs. 9%, P = 0.008). CONCLUSION: The prevalence of clinically relevant cerebral oedema was low (4%) but fatal. Death was attributable to tonsillar herniation. An increased prevalence of ICH was seen in ACLF patients and remains an important differential.

Cutting edge: retrobulbar inflammation, adipogenesis, and acute orbital congestion in a preclinical female mouse model of Graves' orbitopathy induced by thyrotropin receptor plasmid-in vivo electroporation.

Graves' orbitopathy (GO) is a complication in Graves' disease (GD) but mechanistic insights into pathogenesis remain unresolved, hampered by lack of animal model. The TSH receptor (TSHR) and perhaps IGF-1 receptor (IGF-1R) are considered relevant antigens. We show that genetic immunization of human TSHR (hTSHR) A-subunit plasmid leads to extensive remodeling of orbital tissue, recapitulating GO. Female BALB/c mice immunized with hTSHR A-subunit or control plasmids by in vivo muscle electroporation were evaluated for orbital remodeling by histopathology and magnetic resonance imaging (MRI). Antibodies to TSHR and IGF-1R were present in animals challenged with hTSHR A-subunit plasmid, with predominantly TSH blocking antibodies and were profoundly hypothyroid. Orbital pathology was characterized by interstitial inflammation of extraocular muscles with CD3+ T cells, F4/80+ macrophages, and mast cells, accompanied by glycosaminoglycan deposition with resultant separation of individual muscle fibers. Some animals showed heterogeneity in orbital pathology with 1) large infiltrate surrounding the optic nerve or 2) extensive adipogenesis with expansion of retrobulbar adipose tissue. A striking finding that underpins the new model were the in vivo MRI scans of mouse orbital region that provided clear and quantifiable evidence of orbital muscle hypertrophy with protrusion (proptosis) of the eye. Additionally, eyelid manifestations of chemosis, including dilated and congested orbital blood vessels, were visually apparent. Immunization with control plasmids failed to show any orbital pathology. Overall, these findings support TSHR as the pathogenic antigen in GO. Development of a new preclinical model will facilitate molecular investigations on GO and evaluation of new therapeutic interventions.

Prevalence of recurrence and retreatment of ruptured intracranial aneurysms treated with endovascular coil occlusion.

OBJECT: Endovascular coiling is a common treatment for ruptured intracranial aneurysms. However, concerns have been raised over the durability of this treatment. The aim of this study was to establish the rate of recurrence and retreatment of coiled aneurysms treated in our unit. METHODS: We performed a retrospective analysis of 264 surviving patients with ruptured aneurysms treated by endovascular coiling between November 2003 and April 2007. Data was collected on patient age, location of aneurysm, angiogram results and any subsequent retreatment. RESULTS: Follow-up angiography performed at 6 months was available in 239 cases (91%) and revealed 158 (66%) aneurysms completely occluded, 51 (21%) had neck recurrence and 31 (13%) had significant recurrence. Thirty (12.6%) aneurysms required retreatment over a mean follow-up period of 46 (range 24-66) months. Younger age predisposed to a higher risk of recurrence and retreatment. Aneurysms of the anterior communicating and anterior cerebral arteries were less likely to recur or require retreatment (relative risk 0.42 and 0.29, respectively); aneurysms of the posterior communicating arteries were more likely to recur (relative risk 2.22). Aneurysms of the basilar and carotid arteries were more likely to undergo retreatment (relative risk 2.84 and 2.46, respectively). CONCLUSION: Long-term follow-up is required for ruptured aneurysms treated by coiling. Certain subgroups may require closer follow-up due to the increased risk of recurrence or retreatment, such as younger patients and those with aneurysms of the posterior communicating, basilar or carotid arteries.

A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability.

AIM: To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. METHODS: The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP = 362, MSA = 398), 627 had per protocol images (PSP = 297, MSA = 330). Intra-rater (n = 60) and inter-rater (n = 555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n = 441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. RESULTS: Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥ 0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75-0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1-F2; MSA: F2-F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. CONCLUSIONS: The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224.

Vascular neurosurgery following the International Subarachnoid Aneurysm Trial: modern practice reflected by subspecialization.

OBJECT: In this paper the authors' goal was to report on and examine (in the context of a large hospital with good endovascular intervention provisions) the activities of a neurosurgeon with a dedicated vascular interest in the era after the International Subarachnoid Aneurysm Trial in the United Kingdom. They also aimed to establish therapeutic trends and outcomes. METHODS: The authors reviewed the multidisciplinary team activity of 1 neurosurgeon and 2 interventional radiologists during a period of 22 months (2005-2007). They reviewed 281 aneurysm interventions; the majority was used to treat subarachnoid hemorrhage. Data analysis showed a strong preference for endovascular treatment for acute rupture (86.6 vs 13.4%), with a progressively greater role for open microsurgery in the more elective context (57% endovascular vs 43% surgical). They also reviewed 66 interventions for arteriovenous malformations, of which only 6 were surgical. These data are compared against a sample year from 2001 to 2002 (pre-International Subarachnoid Aneurysm Trial), showing comparable rates of surgically treated aneurysms versus endovascularly treated aneurysms, but an increase overall in the number of patients requiring open surgery. RESULTS: The authors found that excellent outcomes for microsurgical clipping compared with endovascular therapy can be achieved within the current climate. These and previously published data strongly support a continuing role for vascular neurosurgery as a subspecialist interest in combination with a dedicated endovascular service and a multidisciplinary team. CONCLUSIONS: Despite a trend to prefer coiling for ruptured aneurysms, the authors have shown that there is still a vital role for open surgery in the management of the ruptured and unruptured aneurysm. They consider the remaining role for surgery for arteriovenous malformations within the modern era of endovascular therapy.

The application of near-infrared oximetry to cerebral monitoring during aneurysm embolization: a comparison with intraprocedural angiography.

Near-infrared spectroscopy (NIRS) has been used to monitor regional cerebral oxygen saturation (rSO2) in patients at risk of cerebral desaturation during surgical and neurointerventional procedures. However, the quantitative capabilities of the method have been questioned, as has its validation compared with jugular bulb oximetry. Here, we compare NIRS data acquired during coil embolization procedures with incidence of vasospasm as detected from angiography. Thirty-two subarachnoid hemorrhage patients underwent embolization. Bilateral SomaSensor strips (Invos 4100, Somanetics) were affixed to the forehead at constant anatomic positions, avoiding frontal sinuses and scalp hair. Mean arterial pressure, SaO2, end-tidal pCO2, temperature and Hb were held within a narrow range during the procedure. Ipsilateral angiography was performed every 10 to 15 minutes. An independent neuroradiologist classified any vasospasm in the parent vessel as mild (25% baseline), moderate (50%), severe (75%), or total (100%). Of all, 15/32 (46.9%) patients developed spasm; in 2 it was severe or total. There was no significant association between World Federation of Neurological Surgeons grade and baseline rSO2 signal (either ipsilateral or contralateral to the side of the aneurysm) (P=0.598). There was no significant association between side of aneurysm and baseline rSO2 signal (P=0.243). However, episodes of angiographic spasm were strongly associated with reduction in trend ipsilateral NIRS signal (P<0.001); furthermore, the degree of spasm (especially more than 75% vessel diameter reduction) was associated with a greater reduction in same-side NIRS signal (P<0.001) (2-level random effects regression model, Stata 8.2, Stata Corp, TX). NIRS may have a useful role to play in the detection of cerebral desaturation secondary to vasospasm during neuroendovascular procedures.

Endovascular trapping of traumatic carotid-cavernous fistulae.

We describe an unconventional endovascular approach to the treatment of traumatic carotid-cavernous fistulas. Four patients with large high-flow shunts have been successfully treated by trapping of the fistula by using a combination of proximal balloon occlusion and distal coil embolization. The latter was achieved following retrograde catheterization of the distal parent vessel via the contralateral carotid or ipsilateral vertebral artery.