The role of surgery when endovascular treatment is considered the first choice therapy for ruptured intracranial aneurysms.

AIM: Nowadays endovascular therapy is more and more considered as first choice treatment for ruptured intracranial aneurysms. The aim of this study was to understand the impact that endovascular treatment (EVT), chosen as first therapeutic strategy, has had in the selection of ruptured intracranial aneurysms submitted to surgery at our Institution and what role neurosurgeons still play in this setting. METHODS: From 1998 to 2002, 272 consecutive patients were treated at the Hospital of Toulouse for ruptured intracranial aneurysms: 222 by embolization and 50 by surgery. The two groups were homogeneous for sex, age and aneurysms multiplicity. RESULTS: The patients of the surgical group had a worst clinical-radiological status at the treatment time than those treated by EVT. Clipping was performed for different reasons: 16% for failure of attempted EVT; 32% for intracranial hematoma requiring surgical evacuation; 30% for aneurysm morphology unsuitable for EVT and 22% for absence of the endovascular operator. Aneurysms of the middle cerebral artery (MCA) represented the main surgical group. The aneurysms judged unsuitable for EVT and addressed to surgery had often a complex morphology representing a challenge also for surgery. Mid-term outcome is significantly better for patients treated by EVT. CONCLUSION: The results show that microsurgery continues to have a role in the treatment of ruptured intracranial aneurysms even when EVT is the first choice. The precarious clinical conditions of the patients submitted to surgery and the frequent complexity of their aneurysms explain their worst outcome. This would advise training dedicated vascular Neurosurgeons to guaranty a high level treatment when EVT is not possible.

Holistic care facilitates seamless transitions for a community-dwelling elder: a case study.

Community-dwelling seniors with declining self-sufficiency are at risk for premature institutionalization. Early intervention while the senior has capabilities is the solution for guiding the elder to appropriate care along the continuum. This article demonstrates how a gerontological nurse as facilitator of healing helped an elder achieve the desired maximum quality of life.

[Decompressive craniectomy and intracranial hypertension]. / Craniectomie décompressive et hypertension intracrânienne.

Decompressive craniectomy was purposed for the treatment of refractory intracranial hypertension after head injury. This review discusses results obtained by this surgery in severe head trauma. Several studies have confirmed a reduction in intracranial pressure secondary to decompressive craniectomy. Mortality decreased and the proportion of good outcome of the survivors increased. These results have not been confirmed prospectively, and indications have to be clarified. The positive effects of decompressive craniectomy compared to barbiturate or hypocapnia in the "second tier therapy" in refractory intracranial hypertension could be interesting to evaluate.

Immunodetection of SV40 large T antigen in human central nervous system tumours.

BACKGROUND/AIMS: DNA sequences from Simian virus 40 (SV40) have been previously isolated from various human tumours of the central nervous system (CNS). This study aimed to investigate a series of tumours of the CNS for the expression of the SV40 large T antigen (Tag), which is an oncogenic protein of the virus. METHODS: A French series of 82 CNS tumours was investigated for Tag expression using a monoclonal antibody and immunohistochemistry. A Tag positive hepatocellular carcinoma cell line from transgenic mice and a kidney biopsy from a patient infected by SV40 were used as positive controls. RESULTS: None of the tumours (20 ependymomas, 20 glioblastomas, 12 oligodendrogliomas, three plexus choroid adenomas, two plexus choroid carcinomas, 15 meningiomas, and 10 medulloblastomas) contained SV40 Tag positive cells. CONCLUSIONS: The lack of SV40 Tag in 82 CNS tumours of various types is at variance with previous studies from different countries, and suggests that the virus may not be an important factor in CNS tumorigenesis, at least in French cases.

Detection of human cytomegalovirus genome and gene products in central nervous system tumours.

Human cytomegalovirus (HCMV) genome and related proteins have been reported in a great proportion of malignant gliomas. However, these results are unexpected since HCMV is not known as an oncogenic virus. By immunohistochemistry (with an anti-IE1 monoclonal antibody) and in situ hybridisation (with biotinylated DNA probes) on tissue microarrays and frozen sections, we investigated a French series of central nervous system (CNS) tumours, including 97 glioblastomas. In 10 cases of glioblastoma, rare astrocyte-like cells, admixed with tumour cells, stained positively for HCMV and in one case a doubtful staining of rare cells was noticed. This may indicate a reactivation of the virus under local immunosuppression but none of the cases of CNS tumours (n=132) contained HCMV genomes and/or proteins in a significant proportion of tumour cells. Our results strongly suggest that HCMV is unlikely to be implicated in the development of human malignant gliomas, at least in French cases.

Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations.

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.

Mutations within the MGC4607 gene cause cerebral cavernous malformations.

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.

Third ventriculocisternostomy in cerebellar haematomas.

BACKGROUND: We prospectively evaluated the role of endoscopic third ventriculocisternostomy in the management of acute obstructive hydrocephalus created by cerebellar hematomas. METHOD: Following a therapeutic diagram based on clinical and radiological signs, endoscopic third ventriculocisternostomy was used to treat hydrocephalus associated with cerebellar hematomas in 8 patients (male: 5, female: 3, mean age: 67 years-old). Causes of cerebellar hemorrhage were spontaneous in 6 cases, traumatic in 1 case, and acute bleeding of a posterior fossa tumor (lung metastasis) in the remaining case. Deeply comatose patients (Glasgow Coma Score between 3 and 5) and patients with signs of brainstem compression were initially excluded from this study. FINDINGS: Overall clinical improvement after third ventriculocisternostomy was achieved in all patients and was associated with the decrease of the ventricle size on follow-up CT scans. One patient who initially had a clot evacuation associated with an external ventricular drainage and persistant hydrocephalus had a successful third ventriculocisternostomy in the post operative course. No complication related to the procedure was noted. INTERPRETATION: In selected patients, third ventriculocisternostomy can be used to treat hydrocephalus associated with posterior fossa hematomas.

Methodological and technical issues for integrating functional magnetic resonance imaging data in a neuronavigational system.

OBJECTIVE: The aim of this article was to analyze the technical and methodological issues resulting from the use of functional magnetic resonance image (fMRI) data in a frameless stereotactic device for brain tumor or pain surgery (chronic motor cortex stimulation). METHODS: A total of 32 candidates, 26 for brain tumor surgery and six chronic motor cortex stimulation, were studied by fMRI scanning (61 procedures) and intraoperative cortical brain mapping under general anesthesia. The fMRI data obtained were analyzed with the Statistical Parametric Mapping 99 software, with an initial analysis threshold corresponding to P < 0.001. Subsequently, the fMRI data were registered in a frameless stereotactic neuronavigational device and correlated to brain mapping. RESULTS: Correspondence between fMRI-activated areas and cortical mapping in primary motor areas was good in 28 patients (87%), although fMRI-activated areas were highly dependent on the choice of paradigms and analysis thresholds. Primary sensory- and secondary motor-activated areas were not correlated to cortical brain mapping. Functional mislocalization as a result of insufficient correction of the echo-planar distortion was identified in four patients (13%). Analysis thresholds (from P < 0.0001 to P < 10(-12)) more restrictive than the initial threshold (P < 0.001) had to be used in 25 of the 28 patients studied, so that fMRI motor data could be matched to cortical mapping spatial data. These analysis thresholds were not predictable preoperatively. Maximal tumor resection was accomplished in all patients with brain tumors. Chronic motor cortex electrode placement was successful in each patient (significant pain relief >50% on the visual analog pain scale). CONCLUSION: In brain tumor surgery, fMRI data are helpful in surgical planning and guiding intraoperative brain mapping. The registration of fMRI data in anatomic slices or in the frameless stereotactic neuronavigational device, however, remained a potential source of functional mislocalization. Electrode placement for chronic motor cortex stimulation is a good indication to use fMRI data registered in a neuronavigational system and could replace somatosensory evoked potentials in detection of the central sulcus.

Effectiveness of conservative management of acoustic neuromas.

OBJECTIVE: The goal of this study was to assess the effectiveness of the conservative management in patients with acoustic neuroma (vestibular schwannoma). STUDY DESIGN: This retrospective study was performed in a university hospital. PATIENTS: Patients were selected for this wait-and-see policy on the basis of age, general condition, audiometric results, tumor size, and patient preference. The study group included 97 patients, 87 of whom had at least two neuroradiologic examinations. The mean age of this population was 63 years (29 to 89 years). The mean length of follow-up of this population was 31 months. Eighty-seven of these patients had at least two radiologic examinations (magnetic resonance imaging or computed tomography). The mean interval between the initial and follow-up radiologic examinations was 15 months. MAIN OUTCOME MEASURES: Tumor size was measured by use of two-dimensional data in all patients. The mean tumor size was 12 mm. The growth rate of the tumor was estimated by comparison of the results of the measurements from the initial and follow-up neuroradiologic examinations. RESULTS: Of the 97 patients studied, 6 patients required surgery and 6 required radiotherapy. Sixty patients (62%) were still being treated conservatively at the end of the study period. Three patients of 28 who were classified as candidates for hearing preservation surgery lost their candidacy during the observation period. The mean annual tumor growth rate was 1.52 mm/year. The tumor was stable in size in 36% of patients, regressed in 11% of patients, or grew in 53% of patients. The growth patterns of the acoustic neuroma fell into five categories: continuous growth in 15% of patients, negative growth in 5%, growth followed by negative growth in 40%, negative growth followed by growth in 20%, and no variation of tumor size in 20%. CONCLUSION: Conservative management of acoustic neuromas carries difficulties: long-term follow-up of the patients and unpredictability of the tumor growth pattern. A reliable and reproducible radiologic method for evaluating tumor size is of great importance.

Functional MRI and intraoperative brain mapping to evaluate brain plasticity in patients with brain tumours and hemiparesis.

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<0.001. These patients, candidates for tumour resection, also underwent cortical intraoperative stimulation that was correlated to the fMRI spatial data using three dimensional reconstructions of the brain. Three patients also had postoperative control fMRI. RESULTS: The absence of fMRI activation of the primary sensorimotor cortex normally innervating the paretic hand for the threshold chosen, was correlated with completely negative cortical responses of the cortical hand area during the operation. The preoperative fMRI activation of these patients predominantly found in the ipsilateral frontal and primary sensorimotor cortices could be related to the residual ipsilateral hand function. Postoperatively, the fMRI activation returned to more classic patterns of activation, reflecting the consequences of therapy. CONCLUSION: In paretic patients with brain tumours, ipsilateral control could be implicated in the residual hand function, when the normal primary pathways are impaired. The possibility that functional tissue still remains in the peritumorous sensorimotor cortex even when the preoperative fMRI and the cortical intraoperative stimulations are negative, should be taken into account when planning the tumour resection and during the operation.

[Importance and limitations of the validation of functional MRI of motor function and language using preoperative cortical stimulation]. / Intérêt et limites de la validation de l'irm fonctionnelle de la motricité et du langage par la stimulation corticale peropératoire.

UNLABELLED: This chapter describes and discusses the value of the localization of functional areas obtained from functional MRI in brain tumor cases. Correlation method is cortical brain mapping by intraoperative stimulation. The experience reported here is focused on the study of motricity and language. METHODS: Twenty two patients with tumors of the rolandic region (n = 16) or in the temporal lobe (n = 6) underwent functional MR mapping and subsequently cortical mapping before tumor resection. The tasks chosen were a flexion and extension of the fingers or a naming task. We used 3D reconstructed images of the surface of the brain to assess intra and post operatively the functional MRI and stimulation data. RESULTS: For the motor correlation, in each case, the results of direct cortical mapping matched those obtained with functional MRI, both positively and negatively, although the extent of the functional activations was larger than the area required to elicit the corresponding movement during intraoperative brain mapping. For the language correlation and for the task chosen, only the results of the precentral areas matched those of functional MRI. CONCLUSIONS: Functional MRI can be used preoperatively to assess motor functional area in patients with rolandic tumors. More studies are needed to validate intraoperatively the language areas and the real extent of functional MRI activations. Finally, the observed discrepancy between functional MRI and cortical stimulation is likely due to the rather profound differences between both techniques, in terms of neurophysiology, practical applications and statistical analysis.

Cortical intraoperative stimulation in brain tumors as a tool to evaluate spatial data from motor functional MRI.

RATIONALE AND OBJECTIVE: The purpose of this prospective, double-blind study was to correlate motor functional MRI (fMRI) with cortical brain mapping by intraoperative stimulation using 3D reconstructed images of the surface of the brain, and to validate the spatial data of fMRI in patients with brain tumors. METHODS: Fourteen patients with tumors of the rolandic region underwent functional MR mapping of the hand region and subsequently cortical mapping before tumor resection. Data obtained with fMRI and brain mapping were not known previously by the neurosurgeon and by the neuroradiologist, respectively (double-blind study). RESULTS: In each case, the results of direct cortical mapping matched those obtained with fMRI, both positively and negatively, although the extent of the functional activations was larger than the area required to elicit the corresponding movement during intraoperative brain mapping. CONCLUSION: fMRI can be used before surgery to assess motor functional area in patients with rolandic tumors. More studies are needed to validate during surgery the real extent of fMRI activations.

Characterization of choline compounds with in vitro 1H magnetic resonance spectroscopy for the discrimination of primary brain tumors.

RATIONALE AND OBJECTIVES: The authors sought to compare 1H magnetic resonance spectroscopy (MRS) spectra from extracts of low-grade and high-grade gliomas, especially with respect to the signals of choline-containing compounds. METHODS: Perchloric acid extracts of six high-grade and six low-grade gliomas were analyzed by 1H MRS at 9.4 Tesla. RESULTS: The signals of glycerophosphocholine (GPC) at 3.23 ppm, phosphocholine (PC) at 3.22 ppm, and choline (Cho) at 3.21 ppm were identified in both types of tumors. The absolute concentrations of all Cho-containing compounds (GPC + PC + Cho) in high-grade and low-grade gliomas were significantly different. The relative contributions of each of the Cho-containing compounds to the total choline signal were also statistically different. For high-grade gliomas, the choline signal is composed of GPC, PC, and Cho in a well-balanced contribution, whereas in low-grade gliomas, the signal is largely due to GPC with a small involvement of PC and Cho. CONCLUSIONS: The differences in the concentration and the repartition of Cho-containing compounds seem to be a marker of high-grade gliomas. They could also help to discriminate between high- and low-grade gliomas in some difficult cases, especially if there is histologic uncertainty between anaplastic astrocytomas and low-grade oligodendrogliomas.

Usefulness of motor functional MRI correlated to cortical mapping in Rolandic low-grade astrocytomas.

The indications for surgery of slow growing tumours like low grade astrocytomas in eloquent areas are difficult. The timing and the benefit/risk ratio of the surgery must be evaluated, taking into account the potential post operative deficit. The purpose of this study was: a) to validate the data obtained with functional MRI (FMRI) by direct cortical stimulation in patients who are candidate for surgery; b) to demonstrate the usefulness of FMRI coupled with cortical brain mapping and 3D reconstructions of the surfaces of the brain in low grade astrocytoma. FMRI of the hand-motor cortex was performed in 8 patients with low grade astrocytomas. They subsequently underwent direct cortical mapping to correlate the results of FMRI and resective surgery sparing the functional area. In the 8 cases, the results of direct cortical mapping in the precentral region matched accurately those obtained from FMRI. When surgical resection of low grade astrocytoma in the motor areas is considered, FMRI used with intra-operative cortical mapping can help the surgeon to spare functional areas during tumour removal.

Prognostic factors in pediatric spinal cord astrocytoma.

BACKGROUND: Factors that could optimize the management of pediatric spinal cord astrocytoma remain unclear and controversial. METHODS: To determine the factors that influence the prognosis of pediatric patients with spinal cord astrocytomas, a series of 73 consecutive patients at 13 French treatment centers with histologically proven spinal cord astrocytomas was retrospectively reviewed. Hospital records, operative records, and results of radiologic investigations were available in all cases. Follow-up was achieved in 94% of cases. RESULTS: Seventy percent of the patients had low grade (1 or 2) tumors. Total or subtotal surgical resection was achieved in 43%. Thirty-six patients were irradiated following surgery. Fifty-one patients were alive at a median follow-up of 54 months. Twenty-three patients relapsed. Univariate analysis showed that good outcome was correlated with male gender, age younger than 7 years, duration of presenting symptoms longer than 2 months, the presence of spinal deformities, and low grade histology, whereas sensory loss was associated with decreased survival. Multivariate analysis using the Cox proportional hazards model confirmed that histology (relative risk [RR] = 7.69) and the interval between first symptoms and diagnosis (RR = 4.93) were significant independent prognostic factors. The extent of surgery or radiotherapy had no clear influence on survival. CONCLUSIONS: This review sheds light on the prognoses of pediatric patients with spinal cord astrocytomas and may help to determine therapeutic strategies based on patients' clinical, radiologic, and pathologic features.

[Presurgical evaluation of cerebral tumors with functional MRI]. / Evaluation pré-chirurgicale des tumeurs cérébrales par IRM fonctionnelle.

PURPOSE: To evaluate the capabilities and the limitations of motor functional magnetic resonance imaging (FMRI) in the presurgical planning of the cerebral tumors located in or near the motor homunculus and to correlate each type of activation with the histologic characteristics of each tumor. MATERIALS AND METHODS: FMRI was performed in 17 patients (14 adults and 3 children), without motor deficit, presenting with various intra cerebral tumors. Three FMRI activation paradigms were used, controlateral to the lesion: ballistic opposition of the fingers, flexion-extension of the foot and click of the tongue. Four patients, without motor deficit, with cerebral tumors far from the motor homunculus were used as control group to look for non specific activations. In all cases, the histopathology of the tumor was known accurately. RESULTS: In 11 patients with infiltrating tumors, the activated areas were clearly displaced. They were often intratumoral and scattered in correlation with the degree of infiltration. Two patients with non infiltrating tumors (meningioma) showed extratumoral shift of the activated areas. Four patients presenting cerebral tumors far from the homunculus motor did not show intratumoral activation. The supplementary motor area and the ipsilateral primary motor cortex were also sometimes activated during the motor tasks. The task of the tongue was often artifacted, probably because of the head motion. CONCLUSIONS: These preliminary results suggest that the histopathologic characteristics of a tumor and especially its microscopic structure plays a role, with others factors, on the motor functional area organization. In a small number of cases, the data obtained from the FMRI could be used intraoperatively, with a neuronavigation system.

Pre-operative and per-operative factors conditioning long-term facial nerve function in vestibular schwannoma surgery through translabyrinthine approach.

Facial nerve function was evaluated in 103 patients, after vestibular schwannoma removal through the translabyrinthine approach. The mean follow-up was 43 months (minimum six months). Grade I facial function was achieved in 100 per cent of stage I schwannomata compared with 36 per cent of stage IV schwannomata. Grade I or II facial function was found in 78 per cent of homogeneous schwannomata, compared with 48 per cent of heterogeneous schwannomata. Facial function was preserved in 89 per cent of cases, if the angle between the internal auditory canal and the schwannoma was > 66 degrees, compared with 54 per cent if the angle was < 66 degrees. There was 82 per cent of normal facial function when the nerve appeared normal after tumour removal, compared with 18 per cent when the nerve was traumatized. When the ratio (stimulation threshold at the internal auditory canal/stimulation threshold at brainstem) was < 2, post-operative facial function was preserved in 87 per cent of cases, compared with 13 per cent when the ratio was > 2.