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In order to identify the cortical areas involved in the reading process and to spare them during surgery, we systematically studied cortical areas by direct cortical stimulation in patients operated on for brain tumours. Seventy-six cortical stimulation mapping studies for language were performed in 35 monolingual and 19 bi- or multilingual patients over a 5-year period. We systematically searched for reading interference areas in addition to standard naming areas using an 'awake surgery' technique for brain mapping. A 'reading aloud' task (translated into different languages in multilingual patients) was used. Brain mapping was performed in left (44 patients) and right (10 patients) hemispheres. Cortical areas involved in reading were identified according to the type of interference, location and distinctness from naming areas. Stimulation of several major hemispheric regions resulted in significant interference with reading aloud: (i) the lower part of the pre- and postcentral gyri (P < 0.00001); (ii) the dominant supramarginal, angular and the posterior part of the superior temporal gyri (P < 0.00001); (iii) in the dominant inferior and middle frontal gyri (P < 0.001); and (iv) in the posterior part of the dominant middle temporal gyrus (P < 0.05). Interferences in reading were generally found in small cortical areas, with intervening areas evoking no reading interferences. Only partial overlap between reading and naming sites was found. Reading-specific sites were preferentially found when stimulating dominant inferior parietal or posterior temporal areas. Different types of reading interferences were noted. While 'articulatory' interferences were found in pre- and postcentral gyri bilaterally, and ocular-induced movements in bilateral middle frontal gyri, paraphasias were found mainly in the dominant supramarginal and posterior superior temporal gyri. Reading arrest sites were found in many regions. Reading interference sites were also occasionally found in the non-dominant hemisphere. In bilingual patients, if common cortical areas could be found, language- and reading-specific areas were sometimes detected, lending support to the concept that bilinguals can have relatively distinct cortical representation of their language skills. Finally, in this series, the location of reading interference sites and their relative specialization showed considerable individual variability.

Cerebral cavernous malformations (CCM) are hamartomatous vascular malformations characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. They cause seizures and focal neurological deficits due to cerebral hemorrhages. CCM loci have already been assigned to chromosomes 7q (CCM1), 7p (CCM2), and 3q (CCM3) and have been identified in 40%, 20%, and 40%, respectively, of families with CCM. Loss-of-function mutations have been identified in CCM1/KRIT1, the sole CCM gene identified to date. We report here the identification of MGC4607 as the CCM2 gene. We first reduced the size of the CCM2 interval from 22 cM to 7.5 cM by genetic linkage analysis. We then hypothesized that large deletions might be involved in the disorder, as already reported in other hamartomatous conditions, such as tuberous sclerosis or neurofibromatosis. We performed a high-density microsatellite genotyping of this 7.5-cM interval to search for putative null alleles in 30 unrelated families, and we identified, in 2 unrelated families, null alleles that were the result of deletions within a 350-kb interval flanked by markers D7S478 and D7S621. Additional microsatellite and single-nucleotide polymorphism genotyping showed that these two distinct deletions overlapped and that both of the two deleted the first exon of MGC4607, a known gene of unknown function. In both families, one of the two MGC4607 transcripts was not detected. We then identified eight additional point mutations within MGC4607 in eight of the remaining families. One of them led to the alteration of the initiation codon and five of them to a premature termination codon, including one nonsense, one frameshift, and three splice-site mutations. All these mutations cosegregated with the disease in the families and were not observed in 192 control chromosomes. MGC4607 is so far unrelated to any known gene family. Its implication in CCMs strongly suggests that it is a new player in vascular morphogenesis.

OBJECTIVE—To support the hypothesis about the potential compensatory role of ipsilateral corticofugal pathways when the contralateral pathways are impaired by brain tumours. METHODS—Retrospective analysis was carried out on the results of functional MRI (fMRI) of a selected group of five paretic patients with Rolandic brain tumours who exhibited an abnormally high ipsilateral/contralateral ratio of activation—that is, movements of the paretic hand activated predominately the ipsilateral cortex. Brain activation was achieved with a flexion extension of the fingers. Statistical parametric activation was obtained using a t test and a threshold of p

Objective To assess the feasibility of synthesis of O -(2-[ 18 F]-fluoroethyl)-L-tyrosine (FET), a new positron emission tomographic (PET) tracer described in several studies but not yet considered standard in management of glioma, in routine practice and to determine FET uptake in a homogeneous group of patients with suspected high-grade glioma. Design Prospective nonrandomized trial. Patients Twelve patients with suspicion of high-grade glioma. Results The mean (SD) FET uptake ratio was 3.15 (0.72) for the 12 patients and 3.16 (0.75) for the 11 patients with glioblastoma. Conclusion The initial results are promising and indicate that FET PET is a valuable and applicable tool for the imaging of high-grade glioma.

Cerebral cavernous malformations (CCMs) are hamartomatous vascular malformations characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. They cause seizures and cerebral hemorrhages, which can result in focal neurological deficits. Three CCM loci have been mapped, and loss-of-function mutations were identified in the KRIT1 (CCM1) and MGC4607 (CCM2) genes. We report herein the identification of PDCD10 (programmed cell death 10) as the CCM3 gene. The CCM3 locus has been previously mapped to 3q26-27 within a 22-cM interval that is bracketed by D3S1763 and D3S1262. We hypothesized that genomic deletions might occur at the CCM3 locus, as reported previously to occur at the CCM2 locus. Through high-density microsatellite genotyping of 20 families, we identified, in one family, null alleles that resulted from a deletion within a 4-Mb interval flanked by markers D3S3668 and D3S1614. This de novo deletion encompassed D3S1763, which strongly suggests that the CCM3 gene lies within a 970-kb region bracketed by D3S1763 and D3S1614. Six additional distinct deleterious mutations within PDCD10, one of the five known genes mapped within this interval, were identified in seven families. Three of these mutations were nonsense mutations, and two led to an aberrant splicing of exon 9, with a frameshift and a longer open reading frame within exon 10. The last of the six mutations led to an aberrant splicing of exon 5, without frameshift. Three of these mutations occurred de novo. All of them cosegregated with the disease in the families and were not observed in 200 control chromosomes. PDCD10, also called “TFAR15,” had been initially identified through a screening for genes differentially expressed during the induction of apoptosis in the TF-1 premyeloid cell line. It is highly conserved in both vertebrates and invertebrates. Its implication in cerebral cavernous malformations strongly suggests that it is a new player in vascular morphogenesis and/or remodeling.

Brain abscesses are associated with high mortality and morbidity even in the antibiotic era and with complex imaging techniques, mainly because of delayed diagnosis. Several reasons can be identified: (1) the incidence of abscesses is low, about 1.1/100 000 person-year1; (2) clinical features may be non-specific without evidence of infection and with neurological signs similar to tumours, which are 50 times more frequent; (3) neuroradiological imaging may be confusing specially in the early stages. The only way to improve the outcome of this pathology is to consider an abscess when faced with a space occupying lesion and to perform a stereotactic biopsy even in elderly or severely deteriorated patients. Recently, in vivo 1H MR spectroscopy (MRS) was reported to give metabolic information on brain abscesses very different from that of brain tumours, permitting a non-invasive differential diagnosis between these two diseases.2 (A) T2 weighted MRI in the axial plane. (B) In vivo1H MRS spectrum from abscess (echo time=135 ms). (C) In vitro 400 MHz 1H MRS spectrum from aspirated pus (aa = aminoacids Ac=acetate, Ala=alanine, Gly=glycine, Lac=lactate, Succ=succinate, Tau=taurine). We report a case in which the diagnosis of an abscess was made on the basis of in vivo 1H MRS resulting in complete …

Seventy-four measurements of cerebral blood flow (CBF) were performed using the Xenon 133 inhalation method in 50 cases of spontaneous subarachnoid hemorrhage. This method is non-traumatic, reproducible and dependable. A correlation was found between clinical condition and CBF values, but in a number of cases which cannot be dismissed, very low mean CBF values or ischemic foci were revealed where clinical state gave no indication of same. A poor correlation appeared between vasospasm seen by angiography and ischemic foci detected by isotopic technique. Patients' age influenced CBF values but not clinical evolution. CBF values, measured in the first two weeks of illness, were significantly higher in those patients having favorable outcome, whatever their clinical state at the time of CBF measurement (comas excluded). The figure of 60 ml/100g/min. for mean cortical flow seemed to be a critical level below which risk of complications was greater. Conversely, in every case where mean cortical flow measured above 70 ml, outcome was favorable. Thus, CBF measurement promises to be a valuable prognostic tool, playing an important role in the therapeutic strategy for this type of patient.