Intracranial Diseases Research Articles

Basic Neuroangiography: Review of Technique and Perioperative Patient Care

Neuroangiography (NA) is an important part of diagnosis and treatment of patients with neurological disease. Although NA may be performed for diagnostic purposes, in many instances NA is performed with the intent to treat. Indications for NA range from extracranial diseases (vertebrobasilar insufficiency from subclavian steal, extracranial carotid stenosis, cavernous-carotid fistula, neck trauma, epistaxis, tumor invasion of the carotid artery, and tumor embolization) to intracranial diseases (nontraumatic subarachnoid hemorrhage, cerebral aneurysms, cerebral arteriovenous malformations, cerebral vasospasm, acute stroke, tumor embolization, and WADA test). Similar to peripheral angiography, appropriate preprocedural assessment and postprocedural care, along with understanding of anatomy, catheter technique, and disease processes, are vital to successful outcomes. This article will review the basic technique, equipment, and patient management in NA. With appropriate skill and knowledge, interventional radiologists can perform NA with safe and successful results.

Moving Vessel Wall Research Beyond the Plaque

The overlap between atherosclerotic disease of the cerebrovascular, cardiovascular, and peripheral vasculature has long been recognized. Carotid atherosclerosis increases the odds of coronary events1 and of finding atherosclerotic changes in coronary, cerebral, aortic, and iliac arteries.2 Similarly, peripheral vascular disease is a risk factor for both stroke and myocardial infarction and is associated with extracranial carotid and intracranial atherosclerosis.3,4 Data from the Reduction of Atherothrombosis for Continued Health (REACH) registry show that atherosclerosis in 1 vascular bed increases the risk of adverse outcomes in each of the other locations, and that multiple disease locations at baseline increase the risk of subsequent cardiovascular and cerebrovascular events.5 Given shared underlying risk factors and pathophysiology, it is not surprising that those who present with atherosclerotic disease in 1 vascular bed are at increased risk for disease in others.6 See accompanying article on page 2240 It is fair to say that although considerable attention has been given to atherosclerotic disease affecting peripheral, cardiac, and carotid arteries, important gaps remain in our knowledge. For example, the intracranial circulation has received comparatively …

Does closure of acid-sensing ion channels reduce ischemia/reperfusion injury in the rat brain?

Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2+-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain and various intracranial diseases. However, the mechanism associated with expression of these channels remains unclear. This study sought to observe the expression characteristics of permeable Ca2+-acid-sensing ion channels during different reperfusion inflows in rats after cerebral ischemia. The rat models were randomly divided into three groups: adaptive ischemia/reperfusion group, one-time ischemia/reperfusion group, and severe cerebral ischemic injury group. Western blot assays and immunofluorescence staining results exhibited that when compared with the one-time ischemia/reperfusion group, acid-sensing ion channel 3 and Bcl-x/l expression decreased in the adaptive ischemia/reperfusion group. Calmodulin expression was lowest in the adaptive ischemia/reperfusion group. Following adaptive reperfusion, common carotid artery flow was close to normal, and the pH value improved. Results verified that adaptive reperfusion following cerebral ischemia can suppress acid-sensing ion channel 3 expression, significantly reduce Ca2+ influx, inhibit calcium overload, and diminish Ca2+ toxicity. The effects of adaptive ischemia/reperfusion on suppressing cell apoptosis and relieving brain damage were better than that of one-time ischemia/reperfusion.

Abcc4 Together with Abcb1 and Abcg2 Form a Robust Cooperative Drug Efflux System That Restricts the Brain Entry of Camptothecin Analogues

Multidrug resistance-associated protein 4 (ABCC4) shares many features with P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), including broad substrate affinity and expression at the blood-brain barrier (BBB). However, the pharmacologic relevance of ABCC4 at the BBB is difficult to evaluate, as most drugs are also substrates of ABCB1 and/or ABCG2. We have created a mouse strain in which all these alleles are inactivated to assess their impact on brain delivery of camptothecin analogues, an important class of antineoplastic agents and substrates of these transporters. Wild-type (WT), Abcg2(-/-), Abcb1a/b(-/-), Abcc4(-/-), Abcb1a/b;Abcg2(-/-), Abcg2;Abcc4(-/-), and Abcb1a/b;Abcg2;Abcc4(-/-) mice received i.v. topotecan, irinotecan, SN-38, or gimatecan alone or with concomitant oral elacridar. Drug levels were analyzed by high-performance liquid chromatography (HPLC). We found that additional deficiency of Abcc4 in Abcb1a/b;Abcg2(-/-) mice significantly increased the brain concentration of all camptothecin analogues by 1.2-fold (gimatecan) to 5.8-fold (SN-38). The presence of Abcb1a/b or Abcc4 alone was sufficient to reduce the brain concentration of SN-38 to the level in WT mice. Strikingly, the brain distribution of gimatecan in brain of WT mice was more than 220- and 40-fold higher than that of SN-38 and topotecan, respectively. Abcc4 limits the brain penetration of camptothecin analogues and teams up with Abcb1a/b and Abcg2 to form a robust cooperative drug efflux system. This concerted action limits the usefulness of selective ABC transport inhibitors to enhance drug entry for treatment of intracranial diseases. Our results also suggest that gimatecan might be a better candidate than irinotecan for clinical evaluation against intracranial tumors.

Unique Remodeling Processes after Vascular Injury in Intracranial Arteries: Analysis Using a Novel Mouse Model

The effectiveness of angioplasty and stenting in intracranial atherosclerotic diseases is controversial due to high rates of delayed restenosis and hemorrhage compared with extracranial arteries. However, the mechanisms underlying these differences are still unclear, because their pathophysiology is yet to be examined. To address this issue, we established a novel vascular injury model in the intracranial internal carotid arteries (IICAs) in mice, and analyzed the remodeling process in comparison to that of the femoral arteries (FAs). In IICAs, neointimal hyperplasia was observed from day 14 and grew until day 56. Although smooth muscle cells (SMCs) emerged in the neointima from day 28, SMCs in the injured media were continuously lost with eventual extinction of the media. Re-endothelialization was started from day 7 and completed on day 28. Accumulation of macrophages was continued in the adventitia until day 56. Compared with FAs, the following points are unique in IICAs: (1) delayed continuous formation of neointima; (2) accumulation of macrophages in the media on day 14; (3) continuous loss of SMCs in the media followed by extinction of the media itself; and (4) continuously growing adventitia. These pathophysiologic differences might be associated with unfavorable outcomes in percutaneous transluminal angioplasty and stenting in intracranial arteries.

Photophobia and bilateral pulvinar involvement in non-alcoholic Wernicke’s encephalopathy

Photophobia is a subjective discomfort to light, varying from mild to intolerable pain, which can be associated with disorders of the anterior eye segment, or intracranial diseases [1]. Although the exact pathophysiology remains obscure, an interaction between the trigeminal nociceptive pathway and the visual system at various brain and ocular levels is accepted [1, 2]. A possible involvement of pulvinar has been recently considered, since it receives both second-order trigeminal neurons projections [3] and direct retinal fibers belonging to the non-visual forming pathway (NVFP) [4, 5]. Wernicke’s encephalopathy (WE) is an acute neurological disorder due to thiamine deficiency, usually involving specific brain areas, such as thalamus and periaqueductal region, also accounted in the pathway of photophobia. Photophobia, however, has never been reported as presenting symptom in WE. Here we report two patients with photophobia as manifesting symptom of non-alcoholic WE, who, beside the involvement of the nociceptive brainstem structures, presented a clear involvement of the pulvinar at brain MRI. The two subjects, respectively, of 70 and 63 years of age, have been described in a review reporting the clinical and MRI findings of ten patients who developed WE after gastrointestinal surgery for cancer [6]. The study was performed according to the Declaration of Helsinki and was approved by the local Ethics Committee. The older patient underwent a surgical procedure of pancolectomy for a colon cancer. One month later, he suddenly became confused, with deterioration of shortterm memory, and asleep. Neurological examination showed horizontal and vertical gaze restriction, mild cerebellar signs as dysarthria and dysmetria, and photophobia. Pupillary diameter was 3 mm they were poor reactive to light and near. Spot light exposure was associated with painful photophobia. Brain MRI evidenced areas of signal alterations in periaqueductal gray, mammillary bodies, medial thalami, both pulvinars, frontal and parietal cortex confirming the diagnosis of WE (Fig. 1a, b). A substitutive therapy with thiamine 300 mg/daily was administrated 2 days after the onset of neurological symptoms. Although the neurological conditions significantly improved with therapy, the patient died for pulmonary complications. The younger subject was diagnosed with a rectal tumor. Ten days after the surgical removal of cancer, he presented with agitation and mental confusion. Neurological examination pointed out cerebellar signs, such as mild dysarthria, dysmetria and gaze-evoked nystagmus, and vertical gaze restriction. Short-term memory was affected. Pupillary diameter was 3.5 mm with poor reactivity and intense F. Rosini E. Pretegiani G. Lucii P. Federighi A. Rufa (&) Eye Tracking and Visual Applications Lab (EVA Lab), Department of Medical, Surgical and Neurological Sciences, University of Siena, Policlinico ‘‘Santa Maria alle Scotte’’, viale Bracci 2, Siena, Italy e-mail: rufa@unisi.it

The Effectiveness of Erlotinib Against Brain Metastases in Non-Small Cell Lung Cancer Patients

Brain metastases commonly occur in non-small cell lung cancer (NSCLC), and patient prognosis is poor. Erlotinib, a specific inhibitor of epidermal growth factor receptor-associated tyrosine kinase, has shown antitumor activity in advanced NSCLC. This study evaluates erlotinib in the treatment for brain metastases from NSCLC. We retrospectively reviewed 40 NSCLC patients with brain metastases. All were treated with oral erlotinib and followed until disease progression, death, or intolerable side effects. EGFR mutations within surgical specimens were retrospectively examined in 9 patients. For intracranial diseases, partial response (PR) was observed in 4 patients (10%), stable disease (SD) in 21 (52.5%), and progressive disease in 15 (37.5%), with an objective response rate of 10% and a disease control rate (DCR) of 62.5%. For extracranial diseases, DCR was observed in 17 patients (42.5%) (3 PRs+14 SDs) and progressive disease in 23 patients (57.5%). DCR within brain lesions in patients with activating EGFR mutations was 80% (1 PR+3 SDs), compared with 25% (1 SD) in patients with negative EGFR mutation. The median progression-free survival and median survival were 3.0 months and 9.2 months, respectively. There were no clinical factors associated with the response to erlotinib and survival as well (all P>0.05), whereas only the DCR in the brain was related to survival in multivariate analysis (P=0.000). Erlotinib is modestly active and well-tolerated by NSCLC patients with brain metastases. Erlotinib seems to be more effective in patients with activating EGFR mutations. Erlotinib may be an alternative to traditional treatments in this patient population.

OPTIMIZING A PROTOCOL FOR 1H‐MAGNETIC RESONANCE SPECTROSCOPY OF THE CANINE BRAIN AT 3T

Intracranial diseases are common in dogs and improved noninvasive diagnostic tests are needed. Magnetic resonance (MR) spectroscopy is a technique used in conjunction with conventional MR imaging to characterize focal and diffuse pathology, especially in the brain. As with conventional MR imaging, there are numerous technical factors that must be considered to optimize image quality. This study was performed to develop an MR spectroscopy protocol for routine use in dogs undergoing MR imaging of the brain. Fifteen canine cadavers were used for protocol development. Technical factors evaluated included use of single-voxel or multivoxel acquisitions, manual placement of saturation bands, echo time (TE), phase- and frequency-encoding matrix size, radiofrequency coil, and placement of the volume of interest relative to the calvaria. Spectrum quality was found to be best when utilizing a multivoxel acquisition with the volume of interest placed entirely within the brain parenchyma without use of manually placed saturation bands, TE = 144 ms, and a quadrature extremity radiofrequency coil. An 18 × 18 phase- and frequency-encoding matrix size also proved optimal for image quality, specificity of voxel placement, and imaging time.

Clinical features and neuroimaging findings of 12 patients with acute disseminated encephalomyelitis involved in corpus callosum

To summarize the clinical features and neuroimaging findings of the patients with acute disseminated encephalomyelitis (ADEM) involved in corpus callosum (CC) so as to distinguish it from other diseases. A total of 12 ADEM patients with the involvement of CC during the period of 2010-2012 were recruited. There were 9 males and 3 females with a mean age of 31±14 years (range: 10-54). Their clinical and neuroimaging features were retrospectively reviewed and all data analyzed by SPSS 18.0. (1) All of them had an acute or subacute onset. Two patients had a history of vaccination and 5 suffered upper respiratory tract infection or diarrhea. (2) The presenting symptoms included fever (n=5), headache (n=4), unsteady gait (n=2), urinary retention (n=1), indifference (n=1) and delirium (n=1). (3) The main clinical symptoms included memory loss (n=9), delirium (n=5), somnolence (n=4), urinary retention (n=9), paraplegia (n=4) and unsteady gait (n=5). (4) The examinations of cerebrospinal fluid (CSF) revealed increased intracranial pressure (n=4), leucocytosis (n=3) and increased protein (n=7) of 7 cases. All oligoclonal bands were negative. (5) The lesions were involved in bilateral CCs in 12 patients. Among them, splenium was the most commonly affected (n=9), secondly stem (n=5) and lastly genu (n=4). For 6 patients, the intracranial lesions were all in their CCs. And among them, 2 cases were involved in spinal cord. Except for CC, there were other focal lesions in brain stem and cerebellum (n=4) and spinal cord (n=6). (6) On magnetic resonance imaging (MRI), all cases showed long T2 signal intensity with blurred images. And among them, 2 cases' lesions in brain were discerned only by diffuse weighing imaging (DWI) or T2 fast fluid-attenuated inversion recovery (T2FLAIR) instead of T2-weighted. The lesions of CCs showed on gadolinium-enhanced MRI were significantly enhanced and the shapes were sheet-like (4/6). Spinal cord lesions was found in 6 cases and most spinal cord lesions were discontinuous. And the number of spinal cord segments with lesions was from 4 to 8. The shapes of lesions of spinal cord showed on enhanced MRI were like thin line. (7) Most of them were misdiagnosed as viral encephalitis (n=5), tuberculous meningoencephalitis (n=1) and brain neoplasms (n=2). And another case was admitted into urology surgery ward due to urinary retention. There are three key points about the characteristics of the ADEM patients with CC lesions: (1) They may have an adult male preponderance. The distinctive symptoms include fever, headache, delirium, somnolence, memory loss, unsteady gait and urination disorders, etc.. (2) The number of lesions on brain MRI can be multiple or single, especially the lesions of CC (mostly in splenium). On MRI, all cases showed long T2 signal intensity with blurred images so that DWI and T2 FLAIR may have a higher efficiency of detecting the lesions. In particular, multiple lesions may be all enhanced or not enhanced at equal pace on enhanced MRI. (3) In ADEM patients with CC lesions, many indices of CSF chemical examination, such as increased intracranial pressure, leucocytosis, increased protein, low sugar and low chloride, indicate the presence of intracranial infective diseases. Therefore they are most likely to be misdiagnosed as viral encephalitis or tuberculous meningoencephalitis. However, CC is not the predilection site for viral encephalitis since CC belongs to white matter but not gray matter. So ADEM should be a more appropriate diagnosis for these cases.

Predictors of in-stent stenosis and occlusion after endovascular treatment of intracranial vascular disease with the Willis covered stent

Covered stent placement has emerged as a promising therapeutic option for intracranial vascular lesions. However, in-stent stenosis and occlusion continue to be important concerns with the use of a covered stent, which is more thrombogenic than other types of stents. The purpose of this study was to determine predictors of in-stent stenosis and occlusion for covered stents used in the treatment of intracranial vascular diseases. Clinical, procedural and angiographic data of 46 patients with 49 intracranial vascular lesions treated with the Willis covered stent (Micro-Port, Shanghai, China) between April 2005 and October 2010 were collected and analyzed retrospectively. Univariate analysis and multivariate logistic regression analysis were performed to determine the factors predictive of in-stent stenosis and/or occlusion of the stents. In-stent stenosis and/or occlusion were documented at angiography in six patients with six lesions, and no stenoses or occlusions were seen at angiography in the remaining 40 patients with 43 lesions. Univariate analysis revealed that hypertension, post-procedure irregular antiplatelet therapy and cerebrovascular arteriosclerosis were associated with in-stent stenosis and/or occlusion. By multivariate logistic regression analysis, post-procedure irregular antiplatelet therapy (odds ratio [OR]=15; 95% confidence interval [CI], 1.172–192.004; p=0.037) and cerebrovascular arteriosclerosis (OR=19; 95% CI, 1.374–262.659; p=0.028) were independent predictors of in-stent stenosis and/or occlusion. Thus, post-procedure irregular antiplatelet therapy and coexistent cerebrovascular arteriosclerosis appear to increase the risk of in-stent stenosis and/or occlusion of covered stents in the treatment of intracranial vascular disease.

Insights into the pathogenesis of takotsubo syndrome, which with persuasive reasons should be regarded as an acute cardiac sympathetic disease entity.

The pathogenesis of takotsubo syndrome (TS) has not been established yet. The literature data dealing with the pathogenesis of TS are abundant but scattered among different medical specialities. Subarachnoid hemorrhage and other acute intracranial diseases and injuries are among the important and currently well-recognized trigger factors for TS. In both induced and spontaneous subarachnoid hemorrhages, signs suggestive of increased cardiac sympathetic overactivity have been documented. Surgical and pharmacological sympathectomy has shown to have protective cardiac effects in both animal and human studies. Increase in local release of norepinephrine from the heart of patients with TS has been measured. Signs of both cardiac sympathetic denervation and myocardial lesions adjacent to the cardiac nerve terminals have been seen. Furthermore, the systematized and typically circumferential pattern of ventricular wall motion abnormality is incongruent with the coronary artery supply region and appears most likely to follow the cardiac sympathetic nerve distribution. In conclusion, compelling literature data support the hypothesis that acute cardiac sympathetic disruption and norepinephrine seethe and spillover is causing TS in predisposed patients. TS is most probably an acute cardiac sympathetic disease entity causing myocardial stunning in which takotsubo is one among other cardiac image study findings.

Successful treatment of macular retinoblastoma with superselective ophthalmic artery infusion

AbstractPurpose To report our experience with superselective ophthalmic artery infusion of Melphalan (SOAIM) for macular retinoblastoma, in order to obtain tumor control while preserving as much as possible useful vision.Methods This report concerns 5 cases with ‘naïve’ unilateral retinoblastoma involving the macula, selected from a group of patients scheduled for SOAIM as the primary treatment. Follow‐up ranged from a minimum of 6 months to a maximum of 30 months.Results Each eye of each patient was treated with a cycle of three SOAIM procedures, made of 3‐5 mg of Melphalan per eye per treatment. SOAIM procedure was well tolerated in all 5 patients. One of the eyes was also treated with cryotherapy while all eyes underwent transpupillary thermo‐therapy and/or argon laser during or after the intra‐arterial treatment cycle. All patients are alive and free of metastatic spread. All the eyes achieved ophthalmoscopic remission of the tumor foci, showing types I to III regression, and no enucleation was necessary.Ultrasounds and fluorangiography were performed.Conclusion SOAIM is effective for the treatment of macular retinoblastoma, when performed in adequate settings by operators with skills in angiographic diagnosis and treatment of intracranial vascular diseases. Moreover, Melphalan selectively delivered in the ophthalmic artery may allow the salvation of eyes which should otherwise be enucleated, showing a very low rate of complications due to local and systemic toxicity.

Etiology of 26 Cases with Progressive Bilateral Sensorineural Hearing Loss

Objective: To reveal the causes of rapidly progressive bilateral sensorineural hearing loss (SNHL), too fast to be age-related degeneration, and too slow to be sudden sensorineural hearing loss. Method: We retrospectively evaluated 26 patients with bilateral progressive HL who visited our hospital from 2007 to 2011. We excluded the patients with bilateral Ménière’ss disease and acute low-tone SNHL from our study. Results: We diagnosed 5 cases with immune-mediated inner ear disease (IMIED) such as vasculitis, 5 with functional HL, 4 with intracranial diseases including nonbacterial meningitis, lymphoma, and siderosis, and 1 with drug-induced HL. We could not identify causes in the remaining 11 cases. HL was one of the first symptoms in 10 of 11 cases with IMIED and intracranial diseases. Treatments including steroid administration achieved significant hearing recovery in 4 cases, including 3 with IMIED and 1 with lymphoma. Conclusion: We revealed that the bilateral progressive HL was often the first symptom of systemic or intracranial diseases. Screening for systemic and intracranial diseases is, thus, important for adequate treatment at early stage of disease.

Changes of anterior fontanel size in children aged 0 - 2 years

To study the development of anterior fontanel(AF) in children less than 2 years of age. The size of AF of the children under 2 years of age was measured. The criteria were: (1) All the children were singletons and term (37 weeks ≤ gestational age ≤ 40 weeks) at birth, birth weight > 2500 g. (3) Those with intracranial diseases (included trauma and asphyxia) and scalp hematoma were ruled out. (3) Healthy children (without intracranial disease, growth retardation, congenital syndrome or bone metabolic diseases such as rickets). (1) The mean value of AF in neonates was 1.5 (0.3 - 2.5) cm, and the average of the AF at 1 month after birth was 2.2 cm, which was the largest one. The size of AF was 1.0 (0.3 - 2.0) cm at age 12 months, and 0.5 (0.3 - 0.7) cm at 24 months. (2) The percentage for the closure of the AF was 3% at 6 months, 26.5% at 12 months, and 93.0% at 24 months. (3) There were no gender differences in the size of the AF (P > 0.05). And the size of AF was not correlated with the development levels of weight, length, and head circumference (P > 0.05). (1) The size of AF at 1 month was maximum (2.2 cm), and then decreased by years. The AF was almost closed (93%) at 24 months. (2) There were no gender differences in anterior fontanel (P > 0.05). The size of AF was not correlated with the growth of weight, length, and head circumferences (P > 0.05). (3) The fontanel dimensions should be represented by oblique diameters of the fontanel in clinical pediatrics. (4) The AF closure time needs to be further evaluated in normal children.

Rewarming: facts and myths from the neurological perspectives

Rewarming: facts and myths from the neurological perspectives

Seizure activity in dogs is associated with enhanced TIMP-2 expression of microglia

In the pathogenesis of epilepsy aberrant synaptic plasticity plays an important role. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are responsible for nervous tissue remodelling resulting in synaptic plasticity in the central nervous system (CNS) and might therefore be crucially involved in epileptogenesis. To assess the potential pathogenetic role of microglial MMPs and TIMPs in seizure induction, twenty-four dogs suffering from different intracranial diseases with and without seizure activity were comparatively examined. Microglial cells were isolated by density gradient centrifugation and their expression profiles of MMP-2, MMP-9, MMP-12, MMP-13, MMP-14, TIMP-1, TIMP-2, and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) were examined via quantitative real-time PCR (qPCR). Interestingly, a significant up-regulation of TIMP-2 expression was found for the first time in dogs suffering from seizures. In conclusion, microglial TIMP expression might be involved in seizure generation.

Abstract 2971: Atheromatous Plaques of the Middle Cerebral Artery in the Lateral Lenticulostriate Artery Territory Infarction

OBJECTIVES: We evaluated the utility of black-blood double inversion recovery magnetic resonance imaging (BBDIR-MRI) for depiction of the intracranial branch atheromatous disease caused by occlusion at the vessel orifices of lager-caliber penetrating arteries. METHODS: BBDIR-MRI was performed on 15 consecutive patients with acute cerebral infarcts in the territories of lateral lenticulostriate arteries, which were classified into small artery occlusion by TOAST criteria. Abnormal wall thickening of the horizontal part (M1) of the middle cerebral artery was considered as the atheromatous plaque causing the occlusion of the vessel orifices. The clinical characteristics including the prevalence of various vascular risk factors, the final size of infarcts and the rate of disease progression were compared between two groups with and without the atheromatous plaque. RESULTS: By BBDIR-MRI, the atheromatous plaques were detected in 8 patiennts (53%), while Time of flight (TOF)-MRA revealed the irregular stenosis in one patient. All of them had the eccentric wall thickening with iso-signal intensity on T1- and T2-weighted images of BBDIR-MRI. The large infarcts exceeding 1.5 cm in diameter tended to be more often in patients with the atheromatous plaque (100%) than those without it (57%). However, there were no significant differences of clinical characteristics between the two groups with and without the atheromatous plaque. CONCLUSIONS: BBDIR-MRI could reveal the atheromatous plaque at M1 portion of the middle cerebral artery more easily than TOF-MRA. It might be useful to distinguish the intracranial branch atheromatous diseases from the other types of infarcts in the territories of lateral lenticulostriate arteries.

Superselective ophthalmic artery infusion of melphalan for intraocular retinoblastoma: preliminary results from 140 treatments

To report our experience in superselective ophthalmic artery infusion of melphalan (SOAIM) for intraocular retinoblastoma. From June 2008 to October 2010, 38 patients (18 women, 20 men; age range at first treatment, 7 months to 22 years) with 41 eyes with retinoblastoma were scheduled for SOAIM, for 17 newly diagnosed retinoblastomas Tumour, Node and Metastasis (TNM) 7th Edition 1a (n = 1), 1b (n = 1), 2a (n = 7), 2b (n = 4) and 3a (n = 4) and 24 retinoblastomas with partial remission/relapse TNM 7th Edition 1b (n = 13), 2a (n = 1) and 2b (n = 10). Eight patients (ten eyes) have been treated by SOAIM alone. Follow-up was 6-27 months in 28 patients (30 eyes). Ophthalmic artery cannulation failed in two patients. Thirty-six patients underwent 140 treatments by internal (n = 112) or external (n = 28) carotid arteries. No major procedural complications occurred. Two patients have been lost to follow-up. Remaining 34 patients (37 eyes) had no metastatic disease. Four patients suffered permanent ocular complications: chorioretinal dystrophy (n = 2), ptosis (n = 1) and strabismus/exotropia (n = 1). Eight (22%) eyes in eight (24%) patients underwent enucleation: 7/16 (43%) newly diagnosed retinoblastomas and 1/22 (4.5%) retinoblastomas undergoing partial remission/relapse. For all treated eyes, Kaplan-Meier eye enucleation-free rates (K-M) were 85.4% (95% CI, 73.3-97.5%), 74.4% (95% CI, 57-91.8%) and still stable at 6, 12 months and 2 years, respectively. For eyes with partial remission/relapse, and eyes at presentation, K-M at 2 years were 95.5% (95% CI, 86.9-100%) and 45.6% (95% CI, 16.6-74.6%), respectively. Superselective ophthalmic artery infusion of melphalan was safe and powerful, especially following other therapies. Superselective ophthalmic artery infusion of melphalan should be added to focal therapies spectrum. In selected cases, melphalan should be combined with other chemotherapeutic agents.

Time to reflect on surgery and neuro-intervention for intracranial atherosclerotic diseases

In view of the early results and halt of recruitment from both the Carotid Occlusion Surgery Study (COSS) and Stenting and the Aggressive Medical Therapy for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study we should seize this opportunity to reflect on future directions, rather than abandoning these procedures, during this period of disillusionment. We here suggest the reasons for the failure of these two clinical trials and review future directions for researche in cerebral revascularization.

Cerebral salt wasting following tuberculous meningoencephalitis in an infant

In patients with central nervous system disease, life-threatening hyponatremia can result from either the syndrome of inappropriate secretion of antidiuretic hormone or cerebral salt wasting. Clinical manifestations of the two conditions may be similar, but their pathogeneses and management protocols are different. Cerebral salt wasting syndrome is a disorder in which excessive natriuresis and hyponatremia occurs in patients with intracranial diseases. We report a 6-month-old girl with CSWS associated with tuberculous meningoencephalitis. She was diagnosed as having CSWS on the basis of hypovolemia, polyuria, natriuresis, and the relatively high level of fractional excretion of uric acid. Aggressive replacement of urine salt and water losses using 0.9% or 3% sodium chloride was done. Fludrocortisone was started at 0.1 mg twice daily on the seventh day of admission and was continued for 17 days.