Long-term efficacy of infliximab on background vascular leakage in patients with Behçet's disease.

PURPOSE: To evaluate the effect of infliximab over the initial 4 years of treatment on inflammatory ocular attacks and background retinal/disc vascular leakage in patients with refractory uveoretinitis associated with Behçet's disease. METHODS: Clinical records of nine patients were retrospectively reviewed. The main outcomes analyzed were frequency of ocular inflammatory attacks, background retinal and disc vascular leakage as assessed by fluorescein angiography during periods of clinical quiescence, best-corrected visual acuity, and adverse effects. RESULTS: The median follow-up on infliximab was 50 months (range 48-58 months). Mean frequency of attacks decreased significantly in years 1, 2, 3, and 4 compared with the baseline 1-year period before infliximab use. Mean background retinal and disc vascular leakage scores also decreased significantly at the end of each 1-year period compared with baseline. Visual acuity improved or was unchanged at the end of 4 years in 17 of 18 eyes. No serious adverse effects were observed. CONCLUSION: Infliximab reduced the mean frequency of ocular attacks and mean background retinal/disc vascular leakage in a long-term sustained manner over 4 years of treatment in Behçet's disease patients.

MicroRNA-34a upregulation during seizure-induced neuronal death.

MicroRNAs (miRNAs) are short, noncoding RNAs that function as posttranscriptional regulators of gene expression by controlling translation of mRNAs. A subset of miRNAs may be critical for the control of cell death, including the p53-regulated miRNA, miR-34a. Because seizures activate p53, and p53-deficient mice are reportedly resistant to damage caused by prolonged seizures, we investigated the role of miR-34a in seizure-induced neuronal death in vivo. Status epilepticus was induced by intra-amygdala microinjection of kainic acid in mice. This led to an early (2 h) multifold upregulation of miR-34a in the CA3 and CA1 hippocampal subfields and lower protein levels of mitogen-activated kinase kinase kinase 9, a validated miR-34a target. Immunoprecipitation of the RNA-induced silencing complex component, Argonaute-2, eluted significantly higher levels of miR-34a after seizures. Injection of mice with pifithrin-α, a putative p53 inhibitor, prevented miR-34a upregulation after seizures. Intracerebroventricular injection of antagomirs targeting miR-34a reduced hippocampal miR-34a levels and had a small modulatory effect on apoptosis-associated signaling, but did not prevent hippocampal neuronal death in models of either severe or moderate severity status epilepticus. Thus, prolonged seizures cause subfield-specific, temporally restricted upregulation of miR-34a, which may be p53 dependent, but miR-34a is probably not important for seizure-induced neuronal death in this model.

Aneurysm ostium angle: a predictor of the need for stent as assistance for endovascular aneurysm coiling in internal carotid artery sidewall aneurysms.

BACKGROUND AND PURPOSE: There is no satisfactory parameter that can predict the need for assistant devices for endovascular aneurysm coiling. Our aim was to evaluate the utility of MOA as a predictor of the need for stent-assisted coiling in ICA sidewall aneurysms. MATERIALS AND METHODS: From a retrospective review of an internal data base, 55 consecutive ICA sidewall aneurysms were identified. Thirty-two of the aneurysms were treated by using endovascular techniques. Because 23 of the 55 aneurysms were either untreated or clipped, 3 experienced interventionalists reviewed the 3D images of these aneurysms and then made a decision as to whether stent-assisted coiling would have been required. Thirty-one of the 55 aneurysms would have required stent-assisted coiling, while 24 would not. Neck width, DNR, AR, and MOA were obtained from each aneurysm by using prototype software. These parameters were then correlated with the requirement of stent-assisted coiling. RESULTS: MOA and neck width of aneurysms requiring stent-assisted coiling were significantly larger than those not requiring stent-assisted coiling (P < .001 and <0.001, respectively). Although the DNR and AR of aneurysms requiring stent-assisted coiling were smaller than those not requiring it, the difference was not significant (P = .22 and 0.12, respectively). ROC analysis revealed that MOA was the parameter that best correlated with the need for stent-assisted coiling. Inclusion of MOA with the rest of the parameters significantly increased the predictive performance regarding the need for stent-assisted coiling (P = .005). CONCLUSIONS: In this small study, MOA was a useful parameter to predict the need for stent-assisted coiling in ICA sidewall aneurysms. Further prospective study of this parameter for aneurysms at multiple locations is required to determine its ultimate value.

Clinical features and visual outcomes of Japanese patients with scleritis.

PURPOSE: To analyse clinical features, systemic associations, treatment and visual outcomes in Japanese patients with scleritis. METHODS: Clinical records of 83 patients with scleritis who presented between 1998 and 2008 to the Ocular Inflammation Service of the Kyorin Eye Center, Tokyo, were reviewed. RESULTS: Of the 83 patients, 57 (69%) had diffuse anterior scleritis, 9 (11%) had nodular anterior scleritis, 8 (10%) had necrotising anterior scleritis and 9 (11%) had posterior scleritis. There was a slight predominance of women (55%) and unilateral disease (53%). Mean age at presentation was 51 years (range 12-82 years). Secondary ocular complications were observed in 78% of patients, including anterior uveitis in 25% and increased intraocular pressure in 40%. Investigation revealed a systemic disease association in 24 patients (29%), including six patients (7.2%) with tuberculosis and 18 patients (22%) with rheumatologic disease. Thirty-five patients (42%) received systemic corticosteroid treatment and 19 patients (23%) received immunosuppressive agents. All 17 patients with necrotising anterior scleritis or posterior scleritis were treated with oral corticosteroids and/or immunosuppressive drugs. Visual outcomes were generally good; however, poorer outcomes were observed in eyes with necrotising scleritis, mostly due to corneal ulceration or corneal opacification. CONCLUSIONS: A systemic disease association was identified in 29% of Japanese patients with scleritis. Roughly one-half of patients received oral corticosteroids and/or immunosuppressive drugs to control inflammation, with generally good visual outcomes.

Endovascular management of vertebral artery dissecting aneurysms: review of 25 patients.

AIM: Management of Vertebral Artery (VA) dissections remains controversial. The clinical and angiographic variables of VA dissections were evaluated to demonstrate the safety and efficacy of endovascular intervention in treatment of VA dissecting aneurysms. MATERIAL AND METHODS: 25 patients with 27 VAdissecting aneurysms were treated with endovascular intervention during the last 10 years.17 patients were admitted with subarachnoid hemorrhage. 23 aneurysms treated using destructive endovascular trapping, while reconstructive techniques were used in 3 aneurysms treated with stent-assisted coiling and one aneurysm treated with false lumen embolization. RESULTS: The right VA was involved in 14 patients, the left VA in 9 patients, while 2 patients had bilateral VA dissection. The pearl and string sign was the commonest angiographic sign in 12 aneurysms. Perioperative complications included; rebleeding in one patient, symptomatic brain stem infarction in two patients and silent cerebellar ischemic lesion in one patient. Afavorable outcome was evident more in patients with unruptured VA dissection (100%) versus (76.5%) in patients presented with SAH. CONCLUSION: The endovascular technique should be individualized according to the clinical status of the patient, angiographic variables, condition of the posterior circulation and the available supplies.

Microarray profile of seizure damage-refractory hippocampal CA3 in a mouse model of epileptic preconditioning.

A neuroprotected state can be acquired by preconditioning brain with a stimulus that is subthreshold for damage (tolerance). Acquisition of tolerance involves coordinate, bi-directional changes to gene expression levels and the re-programmed phenotype is determined by the preconditioning stimulus. While best studied in ischemic brain there is evidence brief seizures can confer tolerance against prolonged seizures (status epilepticus). Presently, we developed a model of epileptic preconditioning in mice and used microarrays to gain insight into the transcriptional phenotype within the target hippocampus at the time tolerance had been acquired. Epileptic tolerance was induced by an episode of non-damaging seizures in adult C57Bl/6 mice using a systemic injection of kainic acid. Neuron and DNA damage-positive cell counts 24 h after status epilepticus induced by intraamygdala microinjection of kainic acid revealed preconditioning given 24 h prior reduced CA3 neuronal death by approximately 45% compared with non-tolerant seizure mice. Microarray analysis of over 39,000 transcripts (Affymetrix 430 2.0 chip) from microdissected CA3 subfields was undertaken at the point at which tolerance was acquired. Results revealed a unique profile of small numbers of equivalently up- and down-regulated genes with biological functions that included transport and localization, ubiquitin metabolism, apoptosis and cell cycle control. Select microarray findings were validated post hoc by real-time polymerase chain reaction and Western blotting. The present study defines a paradigm for inducing epileptic preconditioning in mice and first insight into the global transcriptome of the seizure-damage refractory brain.

Apparent diffusion coefficient of pituitary macroadenoma evaluated with line-scan diffusion-weighted imaging.

OBJECTIVE: The goal of this study was to evaluate the consistency of pituitary macroadenoma using apparent diffusion coefficient (ADC) with line-scan diffusion-weighted imaging (LSDWI). METHODS: Patients with pituitary macroadenoma (n=19) were studied prospectively. The LSDWI was performed using a maximum b factor of 1000 s/mm2. The consistency of macroadenoma was rated as soft, intermediate or hard at transsphenoidal surgery. The ADC values of tumors were compared with the tumor-consistency ratings. RESULTS: A soft consistency was found at surgery in 13 patients (mean ADC: 0.84+/-0.1x10(-3) mm2/s); an intermediate consistency was observed in six patients (mean ADC: 0.81+/-0.16x10(-3) mm2/s). No tumors of hard consistency were found. There was no significant difference in ADC values between tumors of soft consistency compared with tumors of intermediate consistency (P=0.37). CONCLUSIONS: A relationship between tumor consistency and the ADCs of soft and intermediate macroadenomas was not shown in this study using LSDWI.

Percutaneous angioplasty and stenting of subclavian arteries before surgical coronary revascularization in a patient with an aberrant right subclavian artery.

An aberrant right subclavian artery occurs in less than 2% of the population. An associated stenosis of the subclavian artery carries a risk of subclavian-coronary steal in patients who undergo coronary revascularization. We report on the case of a 54-year-old man admitted to our hospital for a coronary artery bypass graft (CABG). Angiographic examination revealed bilateral subclavian-artery stenosis with an aberrant right subclavian artery, anomalous origin of the right vertebral artery from the right common carotid artery, and left vertebral-artery occlusion. The patient underwent successful bilateral subclavian angioplasty and stenting.

Diffusion-weighted MR imaging in carotid angioplasty and stenting with protection by the reversed carotid arterial flow.

BACKGROUND AND PURPOSE: Distal embolism during carotid angioplasty with stent (CAS) can be protected by a flow-reversal device. Diffusion-weighted MR imaging was used to evaluate this protective procedure and perform a comparison with the control. METHODS: Cases of CAS with protection procedures were included in this study. Sixty-five men (68 procedures) and 5 women (5 procedures), with an average age of 68.8 years, having severe carotid stenosis were treated in our department between 2002 and 2004. Eleven cases were treated with the Parodi Anti-Emboli System, with which the internal carotid blood flow is reversed by simultaneous occlusion of the proximal common carotid artery and external carotid artery. Diffusion-weighted MR imaging was performed within 1-3 days after CAS. As controls, data from diffusion-weighted MR imaging in 26 patients who had diagnostic angiography were included. RESULTS: Diffusion-weighted MR imaging in diagnostic angiography showed 11.5% appearance of ischemic spots after procedures. In the Parodi Anti-Emboli System, this value was 18.2%. In the CAS group, ischemic lesions appeared only in the hemisphere ipsilateral to carotid stenosis. There were no ischemic lesions in the opposite carotid or vertebrobasilar territory. The appearance rate of new ischemic spots was not significantly different between the control group and the group of CAS with Parodi Anti-Emboli System (chi2 test, P = .6227, Fisher exact method). CONCLUSIONS: Protection results obtained with the Parodi system were excellent and comparable with conventional angiography.

ProNectin F-grafted-ethylene vinyl alcohol copolymer (EVAL) as a liquid type material for treating cerebral aneurysm--an in vivo and in vitro study.

The authors aimed to develop a liquid material for embolization of aneurysms. In vitro and in vivo performances of the new embolic material were examined by cell culture and using an aneurysm model made in common carotid arteries (CCAs) of adult rats. Engineered protein ProNectin F (PnF), which contains 13 sites of an arginine-glycine-aspartic acid (RGD), was grafted onto ethylene vinyl alcohol copolymer (EVAL-g-PnF). The liquid material, EVAL-g-PnF dissolved in DMSO, was infused into an aneurysm model. The blood segments were harvested 2, 5, and 14 days and examined histologically. A number of bovine coronary artery endothelial cells became able to attach to and form cobblestone-like islands on the EVAL by incorporating PnF. The aneurysm model infused with the EVAL-g-PnF solution revealed that the aneurysm lumen was filled with proliferated fibroblasts and macrophages. On the other hand, the aneurysm model treated with unmodified EVAL showed that the cavity was almost filled with EVAL mass and that fibroblasts and macrophages filled a narrow space between the EVAL mass and the cavity wall. The results indicate that EVAL-g-PnF could be more suitable for reorganizing the cavity of an aneurysm than native EVAL.

Spontaneous haemorrhage into metastatic brain tumours after stereotactic radiosurgery using a linear accelerator.

OBJECTIVE: To determine the incidence and clinical characteristics of spontaneous haemorrhage into metastatic brain tumours after radiosurgery. METHODS: Intratumour haemorrhage rate, clinical features, and treatment were evaluated in 54 patients with 131 brain metastases of varying origin who were treated using linear accelerator radiosurgery. The marginal dose was maintained constant at 20 or 25 Gy, irrespective of tumour size. RESULTS: Haemorrhage was identified in 7.4% of the metastases (five tumours in four patients) before radiosurgery and in 18.5% (10 tumours in 10 patients) after radiosurgery. In three cases, haemorrhage into the tumour after radiosurgery was symptomatic. Half the haemorrhages occurred within one month of radiosurgery. The changes in tumour size observed at the time of haemorrhage were an increase in one tumour, no change in five, and a decrease in four. Haemorrhage into a tumour after radiosurgery was more likely to occur in female patients, in tumours with a larger volume on pretreatment neuroimaging, and in tumours treated with a larger number of isocentres or a higher maximum dose. Haemorrhagic features in the patients or their tumours on presurgical assessment were not disposing factors to haemorrhage after radiosurgery. CONCLUSIONS: When larger brain metastases are aggressively treated by radiosurgery, better local control may be attained but there may also be a higher risk of haemorrhage soon after the treatment.

Seizures arising from the inferior parietal lobule can show ictal semiology of the second sensory seizure (SII seizure).

A 52-year-old right handed man presented with medically intractable partial seizures consisting of numbness on the left upper back spreading to the left upper as well as lower limbs. Head computed tomography and magnetic resonance imaging showed a round calcified lesion in the depth of the superior ramus of the right sylvian fissure. Ictal electrocorticographic recording with chronically implanted subdural electrodes showed low voltage fast activities starting exclusively from an electrode located on the right inferior parietal lobule. No apparent ictal activities were observed from the depth electrodes inserted in the parietal operculum. Somatosensory evoked potentials of 75 ms to 145 ms latency were recorded from the ictal onset zone, which was 2 cm caudal to the perisylvian area corresponding to the second somatosensory area. Seizures arising from the inferior parietal lobule including the angular and supuramarginal gyri can produce partial seizures whose ictal semiology and scalp electroencephalography are indistinguishable from the ones originating from the second somatosensory area.

Repositioning of the vertebral artery with titanium bone fixation plate for trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia is usually treated by the padding method using Teflon felt. However this can not be done in certain cases in whom a large tortuous vertebrobasilar artery compresses the fifth nerve. The transposition method using the sling may be an alternative method. But this method is not an easy procedure and requires a relatively large craniotomy. Two cases were treated by a new and simpler effective technique. CLINICAL PRESENTATION: Two cases of the trigeminal neruralgia were treated. The first case was a 71 year-old male and the second case was a 63 year-old male. The history of the medical treatments were similar and both cases had had trigeminal nerve blocks and were prescribed carbamazepin. However, the pain control was insufficient in both cases. In both cases, three dimensional computerized tomography showed the large tortuous right vertebral artery ran just behind the clivus and compressed the right trigeminal nerve. In the second case past history showed a recent hypertensive cerebellar hemorrhage. TECHNIQUE AND RESULTS: A right suboccipital craniotomy were performed in both cases. In both cases, the right vertebral artery compressed the trigeminal nerve in a rostral direction. The sling technique with nylon sutures was tried in both cases but failed during surgery. Then, the bone fixation stainless plate was cut to 10 cm in length and pre-shaped with pliers. After being shaped, the distal end of the plate was inserted between the vertebral artery and fifth nerve and the proximal end of the plate was fixed to the skull by screw. The fifth nerve was completely isolated from the artery as they were in direct contact. After surgery, the pain disappeared completely during the follow-up of one and a half year in the first case and 9 months in the second case. CONCLUSION: The plate can be bent and curved with plier to suit each individual case. This technique is easily applied even when the slings or other isolation technique is not available and appeared to achieve the mechanically stronger reposition and fixation of a very large and tortuous artery away from the trigeminal nerve.

Splitting and penetration of the optic nerve by an aneurysm arising from the anterior wall of internal carotid artery: case report.

Aneurysms arising from the anterior wall of the internal carotid artery (ICA) are uncommon. There have not been any reports demonstrating the anatomical relation of such aneurysms to the optic nerve. An aneurysm arising from the anterior wall of the ICA splitting and penetrating the optic nerve is reported. A 73 year old woman presented with severe headache due to subarachnoid haemorrhage. She had never experienced a visual disturbance. At surgery, the aneurysm was shown to arise from the anterior wall of the left internal carotid artery and to split and penetrate the left optic nerve. The aneurysm was not related to arterial bifurcation of any branches and was safely neck clipped. Given the evidence of a split and penetration of the optic nerve, the pathogenesis of such an aneurysm may be due to the persistence of an embryonic vessel.

Acoustic neuroma with malignant transformation. Case report.

The authors describe the case of a 57-year-old woman who had a right-sided hearing disturbance that had remained untreated for 1 year. The diagnosis was of a right cerebellopontine angle tumor, and the patient underwent its removal via retrosigmoid approach. Pathologically, the tumor was a typical benign neuroma. Growth of residual tumor was detected 4 years after the initial operation, and it was treated with gamma knife surgery (GKS). Six months later, the tumor had grown, and the patient underwent surgery via a combined retrosigmoid-translabyrinthine approach. Abnormal mitotic figures were observed on histological studies, indicating that the tumor had become malignant. Thereafter, the tumor grew rapidly, and the patient died 6.5 years after the initial treatment. It cannot be ruled out that GKS affected the outcome, but the causal sequence was unclear. Because such a patient is rare, documentation of the case was considered clinically important.

Endovascular occlusion of intracranial aneurysms with Guglielmi detachable coils: correlation between coil packing density and coil compaction.

This retrospective analysis was undertaken to evaluate a possible relationship between coil packing density and coil compaction on intracranial aneurysms embolized using Guglielmi detachable coils (GDCs). Of the patients who underwent endovascular surgery using GDC in our hospital between 1994 and 1998, 33 patients had endovascular treatment with GDC and were examined by follow-up angiography at least 12 months after surgery. They had coil embolization to the extent where aneurysms were no longer filled or only faintly filled as shown by cerebral angiography immediately after surgery. At follow-up angiography, coil compaction was observed in 3 aneurysms. In all patients with coil compaction, the coil packing density was below 20% (14.5 +/- 4.0%). On the other hand, it was over 20% (25.7 +/- 4.7%) in all patients without coil compaction. In the 11 patients with a basilar bifurcation aneurysm, the coil packing density was over 24% and no coil compaction was observed. The coil packing density seems to be one of the critical factors, particularly for predicting whether or not coil compaction will occur. Endovascular surgery should be performed to obtain coil packing density higher than 20%.

Functional mapping of human medial frontal motor areas. The combined use of functional magnetic resonance imaging and cortical stimulation.

Two functional brain-mapping techniques, functional magnetic resonance imaging (fMRI) and cortical stimulation by chronically implanted subdural electrodes, were used in combination for presurgical evaluation of three patients with intractable, partial motor seizures. Brain mapping was focused on characterizing motor-related areas in the medial frontal cortex, where all patients had organic lesions. Behavioral tasks for fMRI involved simple finger and foot movements in all patients and mental calculations in one of them. These tasks allowed us to discriminate several medial frontal motor areas: the presupplementary motor areas (pre-SMA), the somatotopically organized SMA proper, and the foot representation of the primary motor cortex. All patients subsequently underwent cortical stimulation through subdural electrodes placed onto the medial hemispheric wall. In each patient, the cortical stimulation map was mostly consistent with that patient's brain map by fMRI. By integrating different lines of information, the combined fMRI and cortical stimulation map will contribute not only to safe and effective surgery but also to further understanding of human functional neuroanatomy.