The development of the human cerebral cortex is an orchestrated process involving the birth of neural progenitors in the peri-ventricular germinal zones, cell proliferation characterized by both symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in 6 highly ordered, functionally-specialized layers1,2. An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development (MCD)3-6. Mapping of disease loci in putative Mendelian forms of MCD has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WDR62 as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with WDR62 mutations had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mouse and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. WDR62 expression in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the utility of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.

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This study was conducted to describe clinical and prognostic aspects of neurological involvement in Behçet's disease (BD). Patients referred for neurological evaluation fulfilled the criteria of the International Study Group for Behçet's Disease. We analyzed disability and survival by the Kaplan-Meier method, using Kurtzke's Extended Disability Status Scale (modified for BD) and the prognostic effect of demographic and clinical factors by Cox regression analysis. We studied 164 patients; of the 107 diagnostic neuroimaging studies: 72.1% showed parenchymal involvement, 11.7% venous sinus thrombosis (VST) and the others were normal. CSF studies were performed in 47 patients; all with inflammatory CSF findings (n = 18) had parenchymal involvement. An isolated increase in pressure was compatible with either VST or normal imaging. The final diagnoses were VST (12.2%), neuro-Behçet syndrome (NBS) (75.6%), isolated optic neuritis (0.6%), psycho-Behçet syndrome (0.6%), and indefinite (11%). VST and NBS were never diagnosed together. Ten years from onset of BD 45.1% (all NBS) reached a disability level of EDSS 6 or higher, and 95.7 +/- 2.1% of the patients were still alive. Having accompanying cerebellar symptoms at onset or a progressive course is unfavorable. Onset with headache or a diagnosis of VST is favorable. Two major neurological diagnoses in BD are NBS and VST. These are distinct in clinical, radiological, and prognostic aspects, hence suggesting a difference in pathogenesis.

Carotid cavernous sinus fistulas are abnormal communications between the carotid system and the cavernous sinus. Several classification schemes have described carotid cavernous sinus fistulas according to etiology, hemodynamic features, or the angiographic arterial architecture. Increased pressure within the cavernous sinus appears to be the main factor in pathophysiology. The clinical features are related to size, exact location, and duration of the fistula, adequacy and route of venous drainage and the presence of arterial/venous collaterals. Noninvasive imaging (computed tomography, magnetic resonance, computed tomography angiography, magnetic resonance angiography, Doppler) is often used in the initial work-up of a possible carotid cavernous sinus fistulas. Cerebral angiography is the gold standard for the definitive diagnosis, classification, and planning of treatment for these lesions. The endovascular approach has evolved as the mainstay therapy for definitive treatment in situations including clinical emergencies. Conservative treatment, surgery and radiosurgery constitute other management options for these lesions.

BACKGROUND AND PURPOSE:We evaluated the use of MR cisternography after intrathecal administration of gadopentetate dimeglumine to detect the presence and localization of CSF leaks in 19 patients diagnosed with spontaneous intracranial hypotension syndrome according to the criteria of International Headache Society.

Rhombencephalosynapsis is a rare congenital abnormality characterised by dorsal fusion of the cerebellar hemispheres, agenesis or hypogenesis of the vermis, fusion of dentate nuclei and superior cerebellar peduncles. We describe 9 children, aged 1.5 to 6 years, with rhombencephalosynapsis. Isolated rhombencephalosynapsis was found in 2 patients, hydrocephalus in 3 children and another 3 children had ventriculomegaly. Additional supratentorial abnormalities were documented in 5 patients. Clinical findings ranged from mild truncal ataxia and normal cognitive abilities to severe cerebral palsy and mental retardation. No correlation between clinical findings and magnetic resonance imaging could be established so far.

BACKROUND AND PURPOSE:Radiologic identification of the location of the CSF leakage is important for proper surgical planning and increases the chance of dural repair. This article describes our experience in analyzing clinically suspected cranial CSF fistulas by using MR imaging combined with the intrathecal administration of a gadolinium-based contrast agent. MATERIALS AND METHODS:A total of 85 consecutive patients with suspected CSF fistulas who presented with persistent or intermittent rhinorrhea or otorrhea lasting for more than 1 month between 2003 and 2007 were included in this study. RESULTS:We observed objective CSF leakage in 64 of 85 patients (75%). The CSF leak was located in the ethmoidal region in 37 patients (58%), in the superior wall of the sphenoid sinus in 8 patients (13%), in the posterior wall of the frontal sinus in 10 patients (15%), in the superior wall of the mastoid air cells in 6 patients (9%), and from the skull base into the infratemporal fossa in 1 patient (2%). Two patients (3%) showed leakage into Ͼ1 paranasal sinus.CONCLUSIONS: MR cisternography after the intrathecal administration of gadopentate dimeglumine represents an effective and minimally invasive method for evaluating suspected CSF fistulas along the skull base. It provides multiplanar capabilities without risk of radiation exposure and is an excellent approach to depict the anatomy of CSF spaces and CSF fistulas. CSF leakage implies abnormal communication between the subarachnoid space and the nasal or middle ear cavity. It is generally classified as traumatic, nontraumatic (ie, spontaneous), or postsurgical in origin, 1 and most cases are traumatic. Approximately 70% of traumatic CSF fistulas close spontaneously within 1 week after injury without surgical intervention.2-4 However, even in cases of mild CSF rhinorrhea or early spontaneous closure, patients remain at risk of recurrent CSF leakage, pneumocephalus, and infectious meningitis. Precise identification of the location of the CSF fistula allows proper surgical planning, increases the chance of dural repair, and can prevent complications. 5,6 Numerous techniques, including plain skull radiography, intraoperative injection of fluorescein dye, positive contrast (iophendylate) studies, and radionuclide cisternography, are all helpful in limited ways.7-12 MR imaging with T2-weighted sequences has been used to localize CSF fistulas. The demonstration of high-signal-intensity fluid extending from the subarachnoid space directly into the adjacent paranasal sinuses or herniation of the brain into a sinus through a bone defect has been the principal diagnostic criterion.2,13-18 However, some or all of these findings can occasionally be observed in the absence of fistula formation on MR images obtained for reasons other than CSF leakage. The most common method for evaluating a patient with suspected CSF rhinorrhea is a combination of thin-section CT and subsequent CT cisternography (CTC). Although high-resolution CT (HRCT) is sufficient to show bony defects in the skull base...

BACKGROUND AND PURPOSE:Endoluminal reconstruction with flow-diverting stents represents a widely accepted technique for the treatment of complex intracranial aneurysms. This European registry study analyzed the initial experience of 15 neurovascular centers with the Flow-Redirection Intraluminal Device (FRED) system.