Amyloid-related imaging abnormalities-haemosiderin (ARIA-H) in patients with Alzheimer's disease treated with bapineuzumab: a historical, prospective secondary analysis.

BACKGROUND: Amyloid-related imaging abnormalities due to haemosiderin deposition (ARIA-H) occur in patients with mild to moderate dementia due to Alzheimer's disease (AD) and have been reported with increased incidence in clinical trials of amyloid-lowering therapies under development for AD. OBJECTIVE: Our objective was to explore the relationship between the incidences of ARIA-H during treatment with placebo and different doses of bapineuzumab, a humanised monoclonal antibody directed against amyloid ß. METHODS: Two neuroradiologists independently reviewed 2572 GRE/T2* MRI sequences from 262 participants in two phase two clinical trials of bapineuzumab and an open-label extension study. Readers were blinded to the participant's therapy, APOE ε4 genotype and medical history. RESULTS: Several risk factors for small ARIA-H <10 mm (microhaemorrhages) were identified: APOE ε4, bapineuzumab treatment, pre-existing small ARIA-H and use of antithrombotics. The HR (95%CI) for incident ARIA-H <10 mm associated with the number of APOE ε4 alleles was 11.9 (3.3 to 42.5) for 2 versus no alleles and 3.5 (1.0 to 12.0) for 1 versus no allele. The HR for bapineuzumab therapy was 3.5 (1.0 to 12.0); for the presence of baseline ARIA-H <10 mm, it was 3.5 (1.6 to 7.8), and for the use of antithrombotic agents it was 2.2 (1.0 to 4.8). The incidence rate for ARIA-H <10 mm was elevated only in the initial 6 months of active treatment and declined after this interval to a rate similar to that observed in the group treated with placebo. CONCLUSIONS: ARIA-H represents a spectrum of MRI findings due to haemosiderin deposition that appears to be related to impaired vascular integrity. The increased risk for ARIA-H associated with APOE ε4 allele frequency, pre-existing ARIA-H, treatment with bapineuzumab and use of antithrombotic agents provides additional support for this hypothesis of loss of integrity of cerebral vessels due to amyloid burden. TRIAL REGISTRATION: NCT00112073 and NCT00606476.

Imaging pattern of calvarial lesions in adults.

Calvarial lesions often present themselves as clinically silent findings on skull radiographs or as palpable masses that may cause localized pain or soreness. This review aims to explore the radiographic, computed tomography (CT), and magnetic resonance imaging (MRI) characteristics of calvarial neoplastic, inflammatory, and congenital lesions that are common in adults in order to facilitate a structured approach to their diagnosis and limit the differential diagnosis. In addition to reviewing the literature, we reviewed the records of 141 patients of the Montreal Neurological Institute and Hospital with radiologically documented calvarial lesions between 2001 and June 2009. CT is ideal for detecting bony lesions and is helpful in precisely localizing a lesion pre-surgically. MRI is best at identifying intradiploic lesions before they affect the cortical tables and is able to establish extraosseous involvement, especially when paramagnetic contrast is employed.

Low-grade oligodendroglioma: an indolent but incurable disease? Clinical article.

OBJECT: The authors reviewed their institutional experience with pure low-grade oligodendroglioma (LGO), correlating outcomes with several variables of possible prognostic values. METHODS: Sixty-nine patients with WHO-classified LGOs were treated between 1992 and 2006 at the McGill University Health Center. Clinical, pathological, and radiological records were carefully reviewed. Demographic characteristics; the nature and duration of presenting symptoms; baseline neurological function; extent of resection; Karnofsky Performance Scale score; preoperative radiological findings including tumor size, location, and absence/presence of enhancement; and pathological data including chromosome arms 1p/19q codeletion and O-methylguanine-DNA methyltransferase promoter gene methylation status were all compiled. The timing and dose of radio- and/or chemotherapy, date of tumor progression, pathological finding at disease progression, treatment at time of disease progression, and status at the last follow-up were also recorded. RESULTS: The median follow-up period was 6.1 years (range 1.3-16.3 years). The majority (78%) of patients presented with seizures; contrast enhancement was initially seen in 16 patients (25%). All patients had undergone an initial surgical procedure: gross-total resection in 27%, partial resection in 59%, and biopsy only in the remaining 13%. Fifteen patients received adjuvant radiotherapy. Data on O-methylguanine-DNA methyltransferase promoter gene methylation status was available in 47 patients (68%) and in all but 1 patient for 1p/19q status. Survival at 5, 10, and 15 years was 83, 63, and 29%, respectively. Multivariate analysis showed that seizures at presentation and the absence of contrast enhancement were the only independent favorable prognostic factors for survival. The 5-, 10-, and 15-year progression-free survival rates were 46, 7.7, and 0%, respectively. CONCLUSIONS: This retrospective review confirms the indolent but progressively fatal nature of LGOs. Contrast enhancement was the most evident single prognostic factor. New treatment strategies are clearly needed in the management of this disease.

Immediate evaluation of angioplasty and stenting results in supra-aortic arteries by use of a Doppler-tipped guidewire.

Intra-arterial Doppler sonography may complement arteriography by providing immediate physiological evidence of hemodynamic adequacy and by obviating unnecessary angioplastic dilation. We used a Doppler-tipped guidewire in 16 patients and obtained velocity measurements at the site of stenosis immediately before and after carotid artery stenting (CAS) in 10 patients. Intra-arterial Doppler sonography confirmed hemodynamic improvement immediately after stent placement and correlated well with post-CAS duplex Doppler sonography results. Thus, intra-arterial Doppler sonography can be feasibly incorporated into CAS procedures for hemodynamic evaluation and can provide anatomic information that complements information provided by angiography.

Re-growth of a posterior inferior cerebellar artery aneurysm after resection of the associated posterior fossa arteriovenous malformation.

Arteriovenous malformation (AVM)-related aneurysms have been described in the literature. Their behavior varies based on their location in relation to and the activity of the shunting through the index AVM. The intuitive expectation supported by numerous reports is that these aneurysms should regress if the AVM is excluded from the circulation. We describe a case of 46-year-old man who presented with a posterior fossa AVM with an aneurysm on the posterior inferior cerebellar artery feeding the AVM. The nidus of the AVM was successfully excluded by glue embolization, with initial regression of the PICA aneurysm on serial imaging. Five years after the endovascular treatment, the aneurysm showed significant re-growth necessitating endovascular coiling. This case presents the re-growth of an AVM-related aneurysm and emphasizes the importance of long-term follow-up of such aneurysms even if the AVM is completely excluded.

Multi-level Split Cord Malformation: Do We Need a New Classification?

Split cord malformations (SCMs) are thought to be rare abnormalities representing 3.8-5% of all spinal cord anomalies. The prevalence is estimated to be 1 in 5499 live births (0.02%), with a slight female predominance (1.3:1). Although the estimates of prevalence vary, Type I SCM occurs more frequently than Type II SCM. In this paper, we are reporting the clinical presentation and imaging findings of multi-level SCM in a 27-year-old male. A literature review of the embryological background of SCM and pathological hypothesis for this entity is provided. A systematic review has been conducted to identify multi-level SCM cases reported in the literature, followed by proposing a new classification system to further our understanding and management of SCMs.

Communicating hydrocephalus and vestibular schwannomas: etiology, treatment, and long-term follow-up.

Background Large vestibular schwannomas (VSs) can cause hydrocephalus by obstructing the fourth ventricle. Little is known about the communicating hydrocephalus that is seen with a smaller VS. Methods The clinicopathological findings and follow up of three patients with communicating hydrocephalus associated with a small VS are presented. Results Four patients aged 40 to 66 years (mean: 57.7) presented with ataxia, dementia, and urinary incontinence. The VS were 2.0 to 2.4 cm. The cerebrospinal fluid (CSF) protein was elevated in three patients in whom it was measured (1.7 to 6 times normal). The VS was resected in two patients. All of the patients required ventriculoperitoneal shunting (VPS). All of the patients were asymptomatic or improved at follow-up at 9 months to 13 years. Conclusion Communicating hydrocephalus associated with a VS can occur in younger patients than was previously thought. An elevated CSF protein appears to be important, but other factors may be involved. A shunting procedure is often required to relieve the symptoms of hydrocephalus even if the tumor is resected. Possible etiological causes of communicating hydrocephalus in patients with a small VS are discussed.

Volumetric measurement of vestibular schwannoma tumour growth following partial resection: predictors for recurrence.

Vestibular schwannomas (VS) have a higher risk of recurrence following subtotal resection than following near-total resection. We measured tumor remnant growth volumetrically in an attempt to determine potential predictors for postoperative recurrence following subtotal resection. We reviewed the charts of patients who had undergone VS surgery between 1998 and 2007. Thirty patients had an incomplete resection. The principal outcome measure was change in tumor volume (TV) on serial imaging. At a median follow-up of 6.8 years, volumetric measurements showed that 12 patients (40%) developed further tumor growth, while 18 patients remained with stable residual disease. The median rate of growth was 0.53 cm(3)/year. Two-dimensional measurements confirmed growth in only eight of these patients. The postoperative residual TV correlated significantly with subsequent tumor growth (p = 0.038). All patients with residual volumes in excess of 2.5 cm(3) exhibited recurrence. On univariate analysis, only postoperative TV was significantly associated with growth. Median time to failure was 21.5 months. This is the first report of volumetric measurements of VS tumor growth postoperatively. Volumetric measurements appear to be superior to two-dimensional measurements in documenting VS growth and patients with residual tumors >2.5 cm(3) have a significantly higher rate of recurrence.

Supratentorial neurenteric cysts-A fascinating entity of uncertain embryopathogenesis.

The histopathological, immunologic, and ultrastructural findings of neurenteric cysts support an endodermal derivation. These developmental cystic lesions are generally located in the posterior mediastinum, abdomen, and pelvis and may also contain some mesodermal and neuroectodermal elements. In contrast, neurenteric cysts of the central nervous system are very infrequent and occur most commonly in the spinal canal. Intraspinal neurenteric cysts are usually encountered in the cervicothoracic region with an intradural, extramedullary location and are commonly associated with congenital defects of the overlying skin and/or vertebral bodies. Intracranial neurenteric cysts are very uncommon and typically located in the posterior fossa. Several hypotheses have been postulated to explain the origin of intracranial neurenteric cysts. However, the embryologic basis of these fascinating lesions remains incompletely understood. Supratentorial neurenteric cysts are distinctly rare often represent a diagnostic challenge on preoperative neuroimaging. In fact, only 22 cases of supratentorial neurenteric cysts have been reported in the literature including our own patient with a laterally based convexity extraaxial cyst presenting with seizures. In this report, we review the clinical, radiographic, and histological findings of supratentorial neurenteric cysts. We discuss the differential diagnoses and surgical considerations in the management of these intriguing lesions. We also provide an extensive review of normal human embryogenesis and discuss putative mechanisms of embryopathogenesis of supratentorial neurenteric cysts.

Neuromyelitis optica with hypothalamic involvement.

We describe two cases of neuromyelitis optica (NMO) with clinical and radiographically confirmed features of hypothalamic involvement, in the absence of other parenchymal brain lesions. Their course is otherwise typical of Devic's form of NMO. A review of the literature identifies additional cases of NMO in which clinical features attributable to under-recognized dysfunction of the hypothalamic-pituitary axis were present. We propose that the currently accepted criteria for the diagnosis of NMO could be revisited to recognize the possibility of lesions developing within hypothalamic structures.