The role of the immune system in kidney disease.

The immune system and the kidneys are closely linked. In health the kidneys contribute to immune homeostasis, while components of the immune system mediate many acute forms of renal disease and play a central role in progression of chronic kidney disease. A dysregulated immune system can have either direct or indirect renal effects. Direct immune-mediated kidney diseases are usually a consequence of autoantibodies directed against a constituent renal antigen, such as collagen IV in anti-glomerular basement membrane disease. Indirect immune-mediated renal disease often follows systemic autoimmunity with immune complex formation, but can also be due to uncontrolled activation of the complement pathways. Although the range of mechanisms of immune dysregulation leading to renal disease is broad, the pathways leading to injury are similar. Loss of immune homeostasis in renal disease results in perpetual immune cell recruitment and worsening damage to the kidney. Uncoordinated attempts at tissue repair, after immune-mediated disease or non-immune mediated injury, result in fibrosis of structures important for renal function, leading eventually to kidney failure. As renal disease often manifests clinically only when substantial damage has already occurred, new diagnostic methods and indeed treatments must be identified to inhibit further progression and promote appropriate tissue repair. Studying cases in which immune homeostasis is re-established may reveal new treatment possibilities.

Spontaneous subarachnoid hemorrhage and negative initial vascular imaging--should further investigation depend upon the pattern of hemorrhage on the presenting CT?

BACKGROUND: Multiple investigations are usually performed in patients with spontaneous SAH who have negative initial angiography. This study aimed to evaluate the most appropriate use of additional imaging studies and how this may be influenced by the findings of the initial CT. METHODS: A retrospective analysis was performed on a prospectively collected cohort of patients referred with spontaneous SAH and negative initial angiography. The patients were divided into four categories based upon the distribution of blood on the initial CT: perimesencephalic (pSAH), diffuse (dSAH), sulcal (sSAH) and CT negative (CSF positive for xanthochromia) (nCT-pLP). The number and nature of the subsequent imaging investigations were reviewed, and the results were correlated with the findings of the presenting CT. RESULTS: One hundred fourteen patients were included in the study. Repeat imaging found five relevant abnormalities. Three cases of vasculitis were diagnosed on the first DSA following a negative CTA. A case of dissecting aneurysm was revealed on the third neurovascular study. A hemorrhagic spinal tumor presented with xanthochromia. No subsequent abnormality was found on the third DSA or MRI head. No case of pSAH had a subsequent positive finding if the initial CTA was negative. CONCLUSIONS: Certain patterns of SAH are associated with a low yield of abnormalities on repeat imaging if the initial angiography is normal. The authors believe that the pattern of hemorrhage on the presenting CT should be used to guide the most appropriate use of further imaging modalities and present a diagnostic algorithm for this purpose.

3.0 T MRI of 2000 consecutive patients with localisation-related epilepsy.

OBJECTIVES: Clinical guidelines suggest that all patients diagnosed with localised seizures should be investigated with MRI to identify any epileptogenic structural lesions, as these patients may benefit from surgical resection. There is growing impetus to use higher field strength scanners to image such patients, as some evidence suggests that they improve detection rates. We set out to review the detection rate of radiological abnormalities found by imaging patients with localised seizures using a high-resolution 3.0 T epilepsy protocol. METHODS: Data were reviewed from 2000 consecutive adult patients with localisation-related epilepsy referred between January 2005 and February 2011, and imaged at 3.0 T using a standard epilepsy protocol. RESULTS: An abnormality likely to be related to seizure activity was identified in 403/2000 (20.2%) patients, with mesial temporal sclerosis diagnosed in 211 patients. 313/2000 (15.6%) had lesions potentially amenable to surgery. Abnormalities thought unrelated to seizure activity were found in 324/2000 (16.1%), with 8.9% having evidence of ischaemic disease. CONCLUSIONS: Since the introduction of the then National Institute for Clinical Excellence guidelines in 2004, the detection rate of significant pathology using a dedicated 3.0 T epilepsy protocol has not fallen, despite the increased numbers of patients being imaged. This is the largest study of epilepsy imaging at 3.0 T to date and highlights the detection rates of significant pathology in a clinical setting using a high-strength magnet. The prevalence of ischaemic disease in this population is significantly higher than first thought, and may not be incidental, as is often reported.

Cerecyte coil trial: procedural safety and clinical outcomes in patients with ruptured and unruptured intracranial aneurysms.

BACKGROUND AND PURPOSE: This study arose from a need to systematically evaluate the clinical and angiographic outcomes of intracranial aneurysms treated with modified coils. We report the procedural safety and clinical outcomes in a prospective randomized controlled trial of endovascular coiling for ruptured and unruptured intracranial aneurysms, comparing polymer-loaded Cerecyte coils with bare platinum coils in 23 centers worldwide. MATERIALS AND METHODS: Five hundred patients between 18 and 70 years of age with a ruptured or unruptured target aneurysm planning to undergo endovascular coiling were randomized to receive Cerecyte or bare platinum coils. Analysis was by intention to treat. RESULTS: Two hundred forty-nine patients were allocated to Cerecyte coils and 251 to bare platinum coils. Baseline characteristics were balanced. For ruptured aneurysms, in-hospital mortality was 2/114 (1.8%) with Cerecyte versus 0/119 (0%) bare platinum coils. There were 8 (3.4%) adverse procedural events resulting in neurological deterioration: 5/114 (4.4%) with Cerecyte versus 3/119 (2.5%) with bare platinum coils (P = .22). The 6-month mRS score of ≤2 was not significantly different in 103/109 (94.5%) patients with Cerecyte and 110/112 (98.2%) patients with bare platinum coils. Poor outcome (mRS score of ≥3 or death) was 6/109 (5.5%) with Cerecyte versus 2/112 (1.8%) with bare platinum coils (P = .070). For UIAs, there was no in-hospital mortality. There were 7 (2.7%) adverse procedural events with neurological deterioration, 5/133 (3.8%) with Cerecyte versus 2/131 (1.5%) with bare platinum coils (P = .13). There was a 6-month mRS score of ≤2 in 114/119 (95.8%) patients with Cerecyte versus 123/123 (100%) patients with bare platinum coils. There was poor outcome (mRS ≥3 and 1 death) in 5/119 (4.2%) patients with Cerecyte versus 0/123 (0%) patients with bare platinum coils (P = .011). CONCLUSIONS: There was a statistical excess of poor outcomes in the Cerecyte arm at discharge in the ruptured aneurysm group and at 6-month follow-up in the unruptured group. Overall adverse clinical outcomes and in-hospital mortality were exceptionally low in both groups.

Spontaneous closure of a type 2a dural arteriovenous fistula following late recanalization of the occluded sinus.

We describe the rare spontaneous resolution of a type 2a dural AVF that coincided with recanalization of the previously thrombosed sigmoid sinus after ten years of conservative management. The factors potentially responsible for spontaneous fistula obliteration are discussed and the therapeutic implication of this observation is considered.

Symptomatic perianeurysmal edema following bare platinum embolization of a small unruptured cerebral aneurysm.

There is considerable interest in the development of symptomatic inflammatory reactions following coil embolization of cerebral aneurysms. Patients have experienced a range of adverse events, usually after treatment of moderately large aneurysms with modified "bioactive" coils. More recently, it has been recognized that adverse inflammatory reactions can be associated with the use of "nonbioactive" coils, and we present a case of symptomatic perianeurysmal edema after treatment of a small unruptured aneurysm with bare platinum coils.

Extruded aneurysm coils found at craniotomy: report of two cases.

The operative findings are presented in two patients following inadequate coil embolization. At craniotomy, part of the coil mass had extruded through the fundus of both aneurysms. It is unclear if this phenomenon is confined to aneurysms that demonstrate significant regrowth and if there is an increased risk of rebleeding.

The value of radio-anatomical features on non-contrast CT scans in localizing the source in aneurysmal subarachnoid haemorrhage.

Identification of the source of subarachnoid haemorrhage (SAH) can be a challenge in the presence of multiple aneurysms. This study was carried out to assess whether radioanatomical features on noncontrast enhanced computerised tomography (CT) scans may be of value in localizing ruptured intracranial aneurysms. The diagnostic CT scans of 56 consecutive patients, investigated for SAH with cerebral angiography, over a period of six months were available for review. Various radioanatomical features were assessed: (1) pattern of subarachnoid blood (e.g. predominant site and location near major vessel bifurcation), (2) presence of intraparenchymal haematoma, (3) presence of aneurysm contour and (4) hydrocephalus. On the basis of the findings an estimation of the anatomical location of the source of bleeding was made and then compared with the angiogram findings to which the reviewer was blinded. The location of the aneurysm was correctly identified in 89.5% of cases. Careful analysis of the pattern of bleeding was essential for the successful localization of the aneurysm in all these cases. The presence of an aneurysm contour was also associated with correct identification of the source of bleeding (chi(2) = 6.067, P = 0.02). Our findings suggest that radioanatomical features on CT scans in SAH can be a valuable aid in the correct identification of the location of the ruptured aneurysm. This would be of particular significance in the presence of multiple intracranial aneurysms.

Complications of cerebral angiography: a prospective analysis of 2,924 consecutive procedures.

INTRODUCTION: Cerebral angiography is an invasive procedure associated with a small, but definite risk of neurological morbidity. In this study we sought to establish the nature and rate of complications at our institution among a large prospective cohort of consecutive patients. Also, the data were analysed in an attempt to identify risk factors for complications associated with catheter angiography. METHODS: Data were prospectively collected for a consecutive cohort of patients undergoing diagnostic cerebral angiography between January 2001 and May 2006. A total of 2,924 diagnostic cerebral angiography procedures were performed during this period. The following data were recorded for each procedure: date of procedure, patient age and sex, clinical indication, referring specialty, referral status (routine/emergency), operator, angiographic findings, and the nature of any clinical complication or asymptomatic adverse event (arterial dissection). RESULTS: Clinical complications occurred in 23 (0.79%) of the angiographic procedures: 12 (0.41%) significant puncture-site haematomas, 10 (0.34%) transient neurological events, and 1 nonfatal reaction to contrast agent. There were no permanent neurological complications. Asymptomatic technical complications occurred in 13 (0.44%) of the angiographic procedures: 3 groin dissections and 10 dissections of the cervical vessels. No patient with a neck dissection suffered an immediate or delayed stroke. Emergency procedures (P = 0.0004) and angiography procedures performed for intracerebral haemorrhage (P = 0.02) and subarachnoid haemorrhage (P = 0.04) were associated with an increased risk of complications. CONCLUSION: Neurological complications following cerebral angiography are rare (0.34%), but must be minimized by careful case selection and the prudent use of alternative noninvasive angiographic techniques, particularly in the acute setting. The low complication rate in this series was largely due to the favourable case mix.

Stereotactic radiosurgery for brain arteriovenous malformations: quantitative MR assessment of nidal response at 1 year and angiographic factors predicting early obliteration.

INTRODUCTION: We investigated the role of magnetic resonance angiography (MRA) in the early follow-up of patients after stereotactic radiosurgery (STRS) for cerebral arteriovenous malformations (AVMs) and determined the influence of individual morphological factors of AVMs in early response to treatment. METHODS: A group of 40 patients (41 AVMs) consented to a dedicated 1.5-T MR protocol 12 months after receiving STRS for a brain AVM. In addition to standard spin echo sequences, 3-D contrast-enhanced sliding interleaved Ky MRA (CE-SLINKY) and dynamic time-resolved subtraction angiography (MR-DSA) were performed. Nidal volumes were calculated using CE-SLINKY data in patients with a persisting arteriovenous shunt. Planning angiographic data was investigated in all 40 patients. The following AVM factors were used in the statistical analysis to determine their role in nidus obliteration: (1) maximum linear dimension, (2) nidal volume, (3) AVM location (4) nidal morphology, (5) venous drainage, (6) "high-flow angiographic change", (7) prior embolization, and (8) dose reduction. RESULTS: Complete nidal obliteration was found in 9 patients, 26 showed greater than 50% nidal reduction and 6 had less than 50%. Two AVM factors, venous drainage and AVM location, were found to significantly correlate with rate of obliteration. CONCLUSION: We successfully demonstrated the use of MRA to quantitatively assess the response of AVMs to STRS. Two AVM factors, venous drainage and AVM location were found to correlate with rate of obliteration prior to the application of the Bonferroni correction, but if this more rigorous statistical test was applied then none of the factors was found to be significant.

Near fatal haemorrhage 35 years after radiation for laryngeal cancer: emergency embolisation of a vertebral artery aneurysm.

The authors report a rare case of a 75 year old man who presented 35 years after radiotherapy for carcinoma of the larynx, with catastrophic bleeding through the mouth. Both the time and mode of presentation were unusual. The patient required emergency sacrifice of the left vertebral artery to stop the bleeding. The literature has been reviewed.

NK cells mediate costimulation blockade-resistant rejection of allogeneic stem cells during nonmyeloablative transplantation.

Although T-cell CD28/CD40 costimulation blockade represents a powerful mechanism to promote immune tolerance during murine allotransplantation, it has not yet been successfully translated to clinical transplantation. We determined the impact of natural killer (NK) cells on costimulation blockade-resistant rejection of donor bone marrow. We found that NK cells represent a potent barrier to engraftment: host NK depletion led to increased donor stem cell survival, increased mixed hematopoietic chimerism and to engraftment of low doses of donor marrow (1 x 10(8)/kg) that were otherwise rejected. To understand the mechanisms of NK alloreactivity, we employed an in vivo NK-specific cytotoxicity assay. We found that an increased proportion of target cells were killed between days 2 and 8 after cell transfer, and that NK killing of parental targets was inducible: NK cells preprimed with allotargets were more efficient at their elimination upon reexposure. Finally, both transplant and in vivo NK-killing models were used to determine the contribution of LFA-1 to NK alloreactivity. Blockade of LFA-1 led to decreased NK-mediated killing, and increased alloengraftment. These results identify NK alloreactivity as an integral component to costimulation blockade-resistant rejection, and suggest that its inhibition may represent an important target in the clinical translation of tolerance-induction transplantation.

First-line investigation of acute intracerebral hemorrhage using dynamic magnetic resonance angiography.

PURPOSE: To report the initial experience of magnetic resonance (MR) digital subtraction angiography (MR-DSA) in the dynamic assessment of the cerebral circulation in acute non-traumatic intracerebral hemorrhage (ICH). MATERIAL AND METHODS: Twelve patients with acute ICH were investigated within 6 days of the ictus using a dynamic contrast-enhanced 2-D MR angiogram that produces subtracted images with a temporal resolution of 1-2 frame/s. The MR-DSA examinations were assessed for evidence of an intracranial vascular abnormality and were compared with (i) the routine MR sequences, (ii) non-dynamic time-of-flight MR angiography, and (iii) catheter angiogram performed during the same admission. RESULTS: All 12 MR-DSA examinations were considered to be technically satisfactory. MR-DSA detected an intracranial vascular abnormality in 7 patients (3 arteriovenous malformations, 2 aneurysms, 1 dural arteriovenous fistula, and 1 venous thrombosis). All abnormalities were confirmed by catheter angiography with the exception of one patient with venous sinus thrombosis found on MR imaging that did not undergo catheter angiography. All four arteriovenous shunts were detected by MR-DSA by virtue of early venous filling. CONCLUSION: MR-DSA can be performed satisfactorily in the setting of acute ICH and provides an alternative method to catheter angiography for identifying shunting vascular abnormalities such as arteriovenous malformations and fistulae, as well as large aneurysms and venous occlusions. MR-DSA is a contrast-medium-based technique that does not suffer from the T1 shortening effects of acute hemorrhage that can obscure abnormalities on conventional flow-based non-dynamic techniques.

Imaging findings and referral outcomes of rapid assessment stroke clinics.

AIM: A rapid assessment stroke clinic (RASC) was established to provide a rapid diagnostic service to individuals with suspected transient cerebral or ocular ischaemia or recovered non-hospitalized strokes. In this report we review imaging findings and clinical outcomes of patients proceeding to the carotid surgery programme. METHODS: Between October 2000 and December 2002, 1339 people attended the RASC. The findings of head CT and carotid Doppler ultrasound of the 1320 patients who underwent brain and carotid imaging were reviewed, and the number subsequently proceeding to carotid angiography and intervention was reported. RESULTS: CT head scans were normal in 57% of cases; 38% demonstrated ischaemia or infarction; and 3% yielded incidental or other significant findings not related to ischaemia. On screening with carotid Doppler ultrasound, 7.5% showed greater than 50% stenosis on the symptomatic side. A total of 83 patients (6.2%) proceeded to cerebral angiography and 65 (4.8%) underwent carotid endarterectomy or endovascular repair. CONCLUSION: Rapid-access neurovascular clinics are efficient in selecting patients for carotid intervention, but this is at a cost and the number of potential strokes prevented is small. Alternative management pathways based on immediate medical treatment need to be evaluated.

MR imaging of patients with localisation-related seizures: initial experience at 3.0T and relevance to the NICE guidelines.

The purpose of this study is to describe our initial experience of imaging adults with localisation-related epilepsy using MR imaging at 3.0T. We discuss the findings in the context of the recently released NICE guidelines that provide detailed advice on imaging people with epilepsy in the UK. 120 consecutive people over the age of 16 years with localisation-related epilepsy were referred for clinical MR examinations from a regional neuroscience centre in England. None of the people had had MR examinations prior to the present study. High resolution MR imaging was performed taking advantage of the high field strength and high performance gradients of the system. Two experienced neuroradiologists reported on the examinations independently and the presence and type of pathology was recorded. There was complete agreement between the two reporters in all 120 cases. The overall frequency of abnormalities shown by MR was 31/120 (26%) and the commonest abnormality shown was mesial temporal sclerosis found in 10/120 (8%). Tumours were shown in 4/120, all of which appeared low grade as judged by imaging criteria. Epilepsy is the commonest neurological condition and demands a significant resource in order to provide good care for sufferers. Recent guidelines published in the UK have suggested that the majority of people with epilepsy should receive brain MR as part of their routine assessment. Our work shows that using the most sophisticated MR imaging in a highly selected population there is a modest pick-up rate of brain abnormalities. If a widespread epilepsy-imaging programme is started the detection rate is likely to be much lower. Although MR is acknowledged to be a reliable way of detecting pathology in people with epilepsy there is a dearth of information studying the health economics of imaging epilepsy in relation to patient management and outcomes.

Cerebellar abnormalities on proton MR spectroscopy in gluten ataxia.

Gluten sensitivity can manifest with ataxia. The metabolic status of the cerebellum was investigated in 15 patients with gluten ataxia and 10 controls using proton MR spectroscopy. Significant differences were present in mean N-acetyl aspartate levels at short echo time and N-acetyl aspartate/choline ratios at long echo time between the patient and control groups. These data support the hypothesis that cerebellar neuronal physiology differs between patients with gluten ataxia and healthy controls.

Brain arteriovenous malformations: measurement of nidal volume using a combination of static and dynamic magnetic resonance angiography techniques.

Arteriovenous malformations of the brain are complex vascular lesions that are an important cause of death and long-term disability. Currently, catheter angiography (CA) is the reference standard procedure for the diagnosis and follow-up of treated arteriovenous malformations (AVMs). This is an invasive procedure with potential risks. Magnetic resonance angiography (MRA) is commonly used in neurovascular imaging as a non-invasive alternative. Various MRA techniques have been used in the diagnosis and follow-up of AVMs but these have suffered from lack of temporal or spatial resolution. In this 60-patient study we describe the combination of two techniques: dynamic magnetic resonance digital subtraction angiography with a high temporal resolution, and a non-dynamic contrast-enhanced time-of-flight sequence with a high spatial resolution technique, in the assessment of AVM. The results showed an excellent correlation between MRA and CA measurement of both maximum linear dimension and AVM nidus volume.

Hermansky-Pudlak syndrome in a pregnant patient.

Hermansky-Pudlak syndrome is a multisystem disorder with albinism, bleeding diathesis and visual impairment as the main features. We report a case of epidural analgesia in a pregnant patient, who was subsequently discovered to have this syndrome. We believe this to be the first such report.

Neurovascular MRI with dynamic contrast-enhanced subtraction angiography.

The first generation of digital subtraction MR angiography using thick-slab contrast-enhanced 2D projection techniques has confirmed the potential of MRI to produce noninvasive subsecond angiograms of the craniocervical circulation. As time-resolved techniques become more sophisticated and 3D acquisitions can be obtained with high isotropic spatial resolution we may start to see the demise of catheter angiography as a diagnostic procedure.