Neurofilament light chain and profilin-1 dynamics in 30 spinal muscular atrophy type 3 patients treated with nusinersen.

BACKGROUND AND PURPOSE: The aim was to investigate whether neurofilament light chain (NfL) and profilin-1 (PFN-1) might qualify as surrogate disease and treatment-response biomarkers by correlating their concentrations dynamic with clinical status in a cohort of 30 adult spinal muscular atrophy type 3 patients during nusinersen therapy up to 34 months. METHODS: Neurofilament light chain was measured in cerebrospinal fluid at each drug administration with a commercial enzyme-linked immunosorbent assay (ELISA); PFN-1 concentrations were tested in serum sampled at the same time points with commercial ELISA assays. Functional motor scores were evaluated at baseline, at the end of the loading phase and at each maintenance dose and correlated to biomarker levels. The concurrent effect of age and clinical phenotype was studied. RESULTS: Neurofilament light chain levels were included in the reference ranges at baseline; a significant increase was measured during loading phase until 1 month. PFN-1 was higher at baseline than in controls and then decreased during therapy until reaching control levels. Age had an effect on NfL but not on PFN-1. NfL was partially correlated to functional scores at baseline and at last time point, whilst no correlation was found for PFN-1. CONCLUSION: Cerebrospinal fluid NfL levels did not qualify as an optimal surrogate treatment biomarker in adult spinal muscular atrophy patients with a long disease duration, whilst PFN-1 might to a greater extent represent lower motor neuron pathological processes. The observed biomarker level variation during the first 2 months of nusinersen treatment might suggest a limited effect on axonal remodeling or rearrangement.

Lacosamide in monotherapy in BTRE (brain tumor-related epilepsy): results from an Italian multicenter retrospective study.

PURPOSE: Lacosamide (LCM) is a third-generation anti-seizure medication (ASM) approved for focal onset epilepsy in patients aged ≥ 4.378 Previous studies have reported an efficacy of LCM as add-on treatment in brain tumor-related epilepsy (BTRE). To date, there are no studies in the literature focusing on lacosamide used in monotherapy to treat BTRE. In our retrospective study we investigated efficacy and tolerability of LCM in monotherapy in a multicenter national cohort of primary brain tumor patients. METHODS: We collected from 12 Italian Centers 132 patients with primary brain tumors who were treated with LCM in monotherapy. For each patient we evaluated seizure freedom at 3 and 6 months (primary endpoints), side effects and drop-out rate (secondary endpoints). RESULTS: Overall, LCM led to seizure freedom in 64.4% of patients at 3 months and 55% at 6 months. Patients who used two or more ASMs before LCM had a worse seizure control than patients in monotherapy with LCM as first choice. In 14 patients, we observed seizure control despite tumor progression on magnetic resonance (MRI). Multivariate analysis showed that gross-total resection at diagnosis was significantly associated with higher seizure freedom rate at 6 months. Side effects were mainly mild (grade 1-2 according to CTCAE classification) and drop-out rate was low (1.5%). Main side effects were dizziness and somnolence. CONCLUSIONS: This is the first study showing a good efficacy and tolerability of LCM when used in monotherapy in BTRE. Further prospective studies are needed to confirm these preliminary data, investigating also quality of life and neurocognitive functions.

Functional Characterization of the Left Ventrolateral Premotor Cortex in Humans: A Direct Electrophysiological Approach.

In monkeys, motor outputs from premotor cortex (PM) involve cortico-cortical connections with primary motor cortex (M1). However, in humans, the functional organization of PM and its relationship with the corticospinal tract (CST) is still uncertain. This study was carried out in 21 patients undergoing intraoperative brain mapping prior to tumor resection. The left ventrolateral premotor cortex (vlPM-BA6) was identified preoperatively by functional magnetic resonance imaging, and then investigated intraoperatively using high frequency direct electrical stimulation (HF-DES) of the convexity of M1 and vlPM-BA6, with simultaneous recording of motor-evoked potentials (MEPs) from oro-facial, hand and arm muscles. The somatotopy, organization of evoked responses, latency of MEPs, and cortical excitability of vlPM-BA6 were compared with reference data from M1. vlPM-BA6 was found to be less excitable, with significantly longer MEP latencies than M1. In addition to the pure oro-facial and hand-arm muscle representation, a "transition oro-hand zone" was identified in vlPM-BA6. The longer latency of vlPM-BA6 MEPs suggests that human vlPM could act on spinal motoneurons either directly through more slowly conducting CST fibers or via less direct pathways through M1, brainstem, or spinal mechanisms. The results help in disclosing the very different roles of vlPM and M1 in motor control.

No effect of AR polyG polymorphism on spinal and bulbar muscular atrophy phenotype.

BACKGROUND AND PURPOSE: Disease severity varies considerably among patients with Spinal and Bulbar Muscular Atrophy (SBMA). Our aim was to investigate the role of androgen receptor (AR) polymorphic repeats in SBMA phenotype. METHODS: We analyzed the length of AR polyQ and polyG tracts in 159 SBMA patients. RESULTS: No relationship between polyG size or polyG/polyQ haplotypes and clinical phenotype was found. An independent negative correlation between polyQ-length and onset of weakness was confirmed (P < 0.001). CONCLUSIONS: The negative results of our study prompt to continue the search for potential disease modifiers in SBMA outside the AR gene.

Predictive value of inferior fronto-occipital fasciculus (IFO) DTI-fiber tracking for determining the extent of resection for surgery of frontal and temporal gliomas preoperatively.

AIM: This work reports the analysis of the relationship between inferior fronto-occipital fasciculus (IFO), neoplastic lesions and surgical resection, in patients operated for gliomas located in the frontal, temporal and insular lobes of the dominant hemisphere. Aim of the study is evaluating the predictive value of inferior fronto-occipital fasciculus DTI-fiber tracking (FT) for determining the extent of resection preoperatively. METHODS: We selected 38 cases affected by lesions located in the frontal, temporal and insular lobes of the dominant hemisphere, which were related to the trajectory of the IFO. For each patient preoperative and postoperative MR images and DTI-FT were loaded into the neuronavigation system and merged; volumetric scan analysis was used for establishing tumor location and topography, as well as the volume of the lesion and of the residual tumor. All preoperative fiber tracking datasets were evaluated and the position of the tract (IFO) compared to the tumor was recorded. Postoperative MR scans were then compared with DTI-FT, in order to evaluate the correspondence between the resection boundaries and the trajectory of the fiber tract. RESULTS: Amongst the cases in which the IFO was inside the lesion, we found only incomplete resections (5 subtotal and 6 partial resections), while considering the cases in which the IFO was located outside the tumor, it was possible to perform a relevant (total/subtotal) resection in 18 of them (78%). CONCLUSION: FT of the inferior frontal-occipital fasciculus predicts the possibility and the extent of the resection for a frontal, temporal and/or insular lesion of the dominant hemisphere.

Structural morphological characteristics and craniofacial development in macrocephaly-cutis marmorata telangiectatica congenita.

AIM: Macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) is a craniofacial defect secondary to macrosomia; a case is presented in order to increase knowledge of the related complications in particular with respect to craniofacial development. CASE REPORT: The authors report a case of M-CMTC evaluated from the genetic standpoint and that of craniofacial development. The aim was to analyse the patient's clinical development and to plan orthopaedic and surgical treatment, focused on detecting and correcting structural and/or functional maxillomandibular anomalies that are likely to worsen over time. As M-CMTC is a typical morphostructural anomaly found in many patients with macrosomia, increased knowledge of the problem and awareness of the related complications appeared useful so as to tackle them appropriately. Orthopaedic treatment partially corrected the asymmetry and reduced the structural discrepancy, avoiding or at least simplifying surgical treatment on completion of growth.

Welfare impact of improved maize varieties adoption and crop diversification practices among smallholder maize farmers in Ogun State, Nigeria.

In Nigeria, the inconsistency in maize production compared to the projected average output has grave implications considering the sharp increase in maize demand and its strategic importance in addressing economic welfare issues. Thus, emphasis is placed on improved agricultural technologies for increasing farming household's productivity and income. This study explored the determinant of complementary improved maize varieties (IMVs) and crop diversification (CD) adoption on smallholder maize farmers' welfare (measured by productivity and net farm income) in Ogun State, Nigeria, using a cross sectional data obtained from a multi-staged random sampling of 200 respondents. A multinomial endogenous switching regression (MESR), that correct for endogeneity and unnoticed heterogeneity was employed to analysed the data. The results from the analysis highlighted different socioeconomic characteristics, input variables, policy, and institutional variables as the determinants of the package adoption of IMVs and CD. Estimates of the average treatment effect (ATT) from the MESR model revealed that farmers who adopt IMVs and CD in combination or in isolation realised increased maize productivity and net farm income per hectare. However, farmers who adopt only IMVs achieved the highest welfare outcomes. These findings heighten that policies that stimulate IMVs adoption should be designed, prioritised and upscale to farming areas experiencing low yields to meet farmers' socioeconomic and livelihoods conditions.

Long-term effect of anticancer therapy on dentition of Italian children in remission from malignant disease: A cross-sectional study.

AIM: To investigate the effects of anticancer therapy on dental development and caries formation in Italian childhood cancer survivors compared to healthy controls. METHODS: A total of 52 children treated with chemotherapy and/or radiotherapy when younger than 10 years and in remission from at least 2 years, and 52 healthy age- and gender-matched children were consecutively enrolled in this cross-sectional study. All participants were examined for dental caries and enamel defects according to the decayed-missing-filled teeth (dmft/DMFT) index and the Aine rating scale. Panoramic radiographs were taken to estimate dental age and to assess dental abnormalities using the Höltta Defect Index. CONCLUSION: These children are at high risk for tooth developmental abnormalities and poor dental health and should be closely monitored by a specialist dentist.

Combination of temozolomide with immunocytokine F16-IL2 for the treatment of glioblastoma.

BACKGROUND: Glioblastoma patients are still not cured by the treatments available at the moment. We investigated the therapeutic properties of temozolomide in combination with F16-IL2, a clinical-stage immunocytokine consisting of human interleukin (IL)-2 fused to the human antibody F16, specific to the A1 domain of tenascin-C. METHODS: We conducted three preclinical therapy studies, using subcutaneous and intracranial U87MG glioblastoma tumours xenografted in BALB/c nude mice. The same therapeutic schedule was used, consisting of five total administrations every third day, of 0.525 mg temozolomide, 20 microg F16-IL2, the combination, or the control solution. RESULTS: Immunohistochemical analysis of U87MG xenografts and of human glioblastoma specimens showed selective tumour staining of F16. A quantitative biodistribution confirmed the preferential tumour accumulation of radiolabelled F16-IL2. In the study with subcutaneous xenografts, the combination of F16-IL2 with temozolomide induced complete remission of the animals, which remained tumour free for over 160 days. The same treatment led to a consistent size reduction of intracranial xenografts and to a longer survival of animals. The immunocytokine promoted the recruitment of leukocytes into tumours of both models. CONCLUSION: The combined use of temozolomide with F16-IL2 deserves clinical investigations, which will be facilitated by the excellent safety profile in cynomolgus monkeys, and by the fact that F16-IL2 is in clinical trials in patients with cancer.

Guidelines on management of low-grade gliomas: report of an EFNS-EANO Task Force.

BACKGROUND: Diffuse infiltrative low-grade gliomas of the cerebral hemispheres in the adult are a group of tumors with distinct clinical, histological and molecular characteristics, and there are still controversies in management. METHODS: The scientific evidence of papers collected from the literature was evaluated and graded according to EFNS guidelines, and recommendations were given accordingly. RESULTS AND CONCLUSIONS: WHO classification recognizes grade II astrocytomas, oligodendrogliomas and oligoastrocytomas. Conventional MRI is used for differential diagnosis, guiding surgery, planning radiotherapy and monitoring treatment response. Advanced imaging techniques can increase the diagnostic accuracy. Younger age, normal neurological examination, oligodendroglial histology and 1p loss are favorable prognostic factors. Prophylactic antiepileptic drugs are not useful, whilst there is no evidence that one drug is better than the others. Total/near total resection can improve seizure control, progression-free and overall survival, whilst reducing the risk of malignant transformation. Early post-operative radiotherapy improves progression-free but not overall survival. Low doses of radiation are as effective as high doses and better tolerated. Modern radiotherapy techniques reduce the risk of late cognitive deficits. Chemotherapy can be useful both at recurrence after radiotherapy and as initial treatment after surgery to delay the risk of late neurotoxicity from large-field radiotherapy. Neurocognitive deficits are frequent and can be caused by the tumor itself, tumor-related epilepsy, treatments and psychological distress.

Present day's standards in microsurgery of low-grade gliomas.

Low-grade gliomas are slow growing intrinsic lesions that induces a progressive functional reshaping of the brain. Surgical removal of these lesions requires the combined efforts of a multidiscipinary team of neurosurgeon, neuroradiologist, neuropsychologist, neurophysiologist, and neurooncologists that all together contribute in the definition of the location, extension, and extent of functional involvement that a specific lesion has induced in a particular patient. Each tumor has induced particular and specific changes of the functional network, that varies among patients. This requires that each treatment plan should be tailored to the tumor and to the patient. When this is reached, surgery should be accomplished according to functional and anatomical boundaries, and has to aim to the maximal resection with the maximal patient functional preservation. This can be reached at the time of the initial surgery, depending on the functional organization of the brain, or may require additional surgeries, eventually intermingled with adjuvant treatments. The use of so called brain mapping techniques extend surgical indications, improve extent of resection with greater oncological impact, minimization of morbidity and increase in quality of life. To achieve the goal of a satisfactory tumor resection associated with the full preservation of the patients abilities, a series of neuropsychological, neurophysiological, neuroradiological and intraoperative investigations have to be performed. In this chapter, we will describe the rationale, the indications and the modality for performing a safe and rewarding surgical removal of low-grade gliomas by using these techniques, as well as the functional and oncological results.

Vitamin D at term of pregnancy and during lactation in white and black women living in Northern Italy.

AIM: Evaluate the vitamin D serum status in a population of white and black mothers who live in the same geographic area of northern Italy (45 degrees 8' N of latitude) and its correlation with vitamin D serum concentrations of the respective newborns at birth, at 2 and 12 months. METHODS: Twelve white woman-infant pairs and 12 black woman-infant pairs were recruited from January through March 2006. The study population had no pre-existing disease and delivered at term of pregnancy (37-41 weeks of gestational age). Only black infants were given vitamin D supplementation from birth to 1 year of age. RESULTS: Eleven black and 12 white women had low vitamin D serum levels at term of pregnancy. Similarly, black and white newborns were both vitamin D deficient at birth. After 12 months white women re-gained physiological vitamin D serum levels, whereas black women maintained a status of vitamin D deficiency. Black newborns who were given supplementation showed lower vitamin D serum concentrations as compared with white newborns at 1 year of age. CONCLUSION: These data showed that all the women living in the same region of northern Italy without any supplementation are equally vitamin D deficient at term of pregnancy regardless of their skin pigmentation. Consequently, every woman should be supplied with additional vitamin D during pregnancy and lactation, though such supplementation seems to exert the most beneficial effects in black women.

Descending necrotizing mediastinitis. Two cases consequent on odontogenic infections and a review of literature.

Mediastinitis is a frequently-fatal infection of the connective tissue that surrounds the mediastinal organs. The principal causes are perforation of the oesophagus or infections following thoracic surgery with sternotomy, but it may also occur as a rare but dangerous complication of oropharyngeal or cephalic infections that, spreading through the fascias of the cervical spaces, reach and infect the connective tissue present in the mediastinum and between the pleura. The chief cause of the high rate of mortality still carried by this disease is the poor understanding of this possible complication of oro-facial infections (sometimes initially trivial) and the consequent delay in diagnosis and failure to provide adequate therapy. Mediastinal infections of odontogenic aetiology is a rare occurrence but its management requires an early diagnosis and an aggressive surgical treatment. So all the dentists and the oral surgeons should consider the possibility of onset of this dangerous complication also of banal infections of mandibular molars. The aim of this article is to review the literature, and to report two cases of patients whom, following on to odontogenic infections originating from molars in the mandibular arch, developed an odontogenic cervical abscess complicated by pleural effusion, mediastinal empyema and septic shock, with severe risk of a fatal outcome.

The effect of an oral spray containing an aqueous extract of Triticum vulgare on dental plaque and gingival inflammation in schoolchildren: A randomized controlled trial.

AIM: To investigate whether the daily use of a spray containing an aqueous extract of Triticum vulgare (TV), belonging to the family of Graminaceae, associated with supervised toothbrushing may improve gingival health in schoolchildren with mixed dentition. MATERIALS AND METHODS: Study design: Randomised, controlled, single-centre, examiner blind, parallel-group study. The study population included 57 schoolchildren with plaque-induced gingivitis randomly allocated to test (n = 29) and control (n = 28) group. Both groups were enrolled in a mechanical plaque control programme for a period of 2 weeks. The test group was also instructed to use a gluten free spray formulation of TV spray twice daily after toothbrushing. Evaluations of plaque index, modified gingivitis index (GI), salivary pH and whole stimulated saliva quantity took place at baseline and after 1 and 2 weeks of study product use. RESULTS: No side effects were observed. Plaque accumulation and GI statistically significantly improved compared with baseline in both groups (all P-values < 0.005), while salivary pH remained nearly unchanged. Between-group differences in index reduction were statistically significant only for GI favouring the test group (P = 0.013). STATISTICS: Repeated-measures ANOVA and the Friedman test were applied to evaluate the influence of time on quantitative variables within each treatment group. Differences between test and control groups were tested using the unpaired t test or the Mann-Whitney U-test with Bonferroni correction. CONCLUSIONS: This study found that TV in spray formulation is safe and effective in controlling gingival inflammation. Thus, it may be a potential adjuvant in the treatment of gingivitis in combination with mechanical plaque control in schoolchildren.

Prevalence of some hepatitis B virus markers among pregnant women attending antenatal clinic in Specialist Hospital Sokoto Nigeria.

BACKGROUND: Hepatitis B virus infection is a global public health problem. The virus has infected more than one-third of the global population. It has been estimated that 360 million chronic carriers are living around the world with a high risk for developing cirrhosis, hepatic carcinoma and hepatic failure. OBJECTIVE: The aim of this study was to determine the prevalence of some hepatitis B markers among pregnant women attending antenatal clinic in Sokoto Specialist Hospital, Nigeria. METHODS: The hepatitis testing was carried out using the Skytec-Rapid Diagnostic HBV-5 rapid kit (Skytec-Rapid Diagnostic, USA). The kit is based on lateral flow chromatographic immunoassay for the qualitative detection of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb in human serum or plasma. Panel format can conveniently test for five targets at once and utilizes all markers to help distinguish between acute and chronic infections. RESULTS: Out of 117 pregnant women tested, 15 were positive for HBsAg (12.8%), 6 positive for HBsAb (5.1%), 1 for HBeAg (0.9%), 14 tested positive for HBeAb (12.0%), and 14 tested for HBcAb (12.0%). The prevalence of HBsAg, HBsAb, HBeAg, HBcAb and HBcAb was compared based on ethnicity. HBsAb was significantly higher among the Hausa ethnic group (p= 0.001). The prevalence of HBsAb, HBeAg, HBcAb and HBcAb was not affected by ethnicity (p> 0.05). The prevalence of HBsAg, HBsAb, HBeAg, HBcAb and HBcAb was compared based on age. Infection by the hepatitis B virus markers was higher among young adult and middle age groups. The difference was however not statistically significant (p> 0.05). The prevalence of HBsAg, HBsAb, HBeAg, HBcAb and HBcAb was compared based on the educational status, previous history of blood transfusion, jaundice, employment status and previous history of still births among the pregnant subjects. There were no statistically significant differences in the prevalence of Hepatitis B virus markers (p> 0.05). CONCLUSION: The study observed a high prevalence of various hepatitis B viral markers among pregnant women attending antenatal care in Specialist Hospital Sokoto. There is need for routine screening of all pregnant women and infants born to hepatitis B positive mothers. Government and non-governmental organizations should intensify efforts to enlighten the general population on the public health importance of the disease and the importance of hepatitis screening. There is also need for the development of a treatment protocol for the management of pregnant women positive for hepatitis B to prevent mother to child transmission. There is an urgent need for the implementation of evidenced-based best practice of providing universal vaccination against hepatitis B for all hepatitis B negative women of child bearing age in particular and all Nigerians in general.

Mitochondrial disorders of the nuclear genome.

BACKGROUND: Mitochondrial myopathies are regulated by two genomes: the nuclear DNA, and the mitochondrial DNA. While, so far, most studies have dealt with mitochondrial myopathies due to deletions or point mutations in the mitochondrial DNA, a new field of investigation is that of syndromes due to mutations in the nuclear DNA. These latter disorders have mendelian inheritance. RESULTS: Three representative cases have been selected: one with COX deficiency and a Leigh syndrome due to a SURF1 gene mutation, one due to a defect of Coenzyme Q synthesis and one with dominant optic atrophy due to a mutation in the OPA1 gene. CONCLUSIONS: Future developments will show that many neurodegenerative disorders are due to mutations of nuclear genes controlling mitochondrial function, fusion and fission.

Defective recognition and naming of famous people from voice in patients with unilateral temporal lobe tumours.

Twenty-nine patients who underwent surgery for a temporal glioma, either in the left (16 patients) or right (13 patients) hemisphere, were administered standardized tests of unknown voice discrimination (UVD) and of famous voice recognition (VO-REC), which included tasks of familiarity evaluation, semantic identification and naming of famous voices. The UVD consisted of twenty stimuli, in which two audio files were consecutively presented; the subject was requested to judge whether the voices belonged to the same or different persons. In the VO-REC, patients were requested to recognize the voices of 40 very well known people; these voices were intermingled with the voices of 20 unknown people for a familiarity check, followed by identification and naming of persons recognized as familiar. We aimed at verifying the effect of laterality and intra-temporal site of lesion on familiarity assessment, false alarms, identification and naming of familiar people. As for the effect of lesion side, our results showed that patients with right temporal gliomas were significantly more impaired in voices discrimination and produced more false alarms than patients with a left glioma, who, in turn, were significantly more impaired in name retrieval than patients with a right temporal glioma. The high number of false alarms in patients with a right temporal glioma suggests that familiarity judgment was impaired. Regarding the neuroanatomical correlates of these different patterns of impairment, MRI data suggested that: (a) UVD disorders are due to lesions involving the whole right anterior temporal lobe and extending to lateral portions of the temporal and frontal lobes; (b) familiarity judgments (testified by an increased number of false alarms) are impaired in lesions restricted to the right anterior temporal lobe; (c) name retrieval deficits are found only in patients with left temporal lesions. UVD disorders were interpreted, at least in part, as due to an impairment of executive functions, resulting from a disconnection of the right temporal lobe from the frontal lobe control. A partly unexpected finding was that some patients with a right temporal tumour had a normal performance in famous voice recognition and identification, in spite of having severe voice discrimination disturbances. These unexpected results, in agreement with previous observation made in the visual (face) modality, are inconsistent with strictly hierarchical models of voice processing.

Cortical and subcortical motor mapping in rolandic and perirolandic glioma surgery: impact on postoperative morbidity and extent of resection.

AIM: Surgery for gliomas located inside or in proximity of motor cortex or tracts requires cortical and subcortical mapping to locate motor function; direct electrical stimulation of brain cortex or subcortical pathways allows identification and preservation of motor function. In this study we evaluated the effect which subcortical motor mapping had on postoperative morbidity and extent of resection in a series of patients with gliomas involving motor areas or pathways. METHODS: One hundred and forty-six patients were included in the study. Intraoperative findings of primary motor cortex or subcortical tracts were reported, together with incidence of new postoperative deficits at short (1 week) and long term (1 month) examination. The relationship between intraoperative identification of subcortical motor tracts and extent of resection was reported. RESULTS: The motor strip was found in 133 patients (91%) and subcortical motor tracts in 91 patients (62.3%). New immediate postoperative motor deficits were documented in 59.3% of patients in whom a subcortical motor tract was identified intra-operatively and in 10.9% of those in whom subcortical tracts were not observed; permanent deficits were observed in 6.5% and 3.5%, respectively. A total resection was achieved in 94.4% of patients with high-grade gliomas and in 46.1% of those with low-grade gliomas.

Review of language organisation in bilingual patients: what can we learn from direct brain mapping?

Although the majority of people worldwide are bilingual, the brain representation of language in bilingual persons is still a matter of debate. Since the beginning of the studies conducted on bilinguals, most authors denied that learning a new language requires a new semantic processing or the involvement of new cortical areas. In this paper, we review neurosurgical studies using direct electrocortical or subcortical stimulation techniques for brain mapping in bilingual subjects and compare this data with that obtained from other brain mapping methods. The authors focused on the most controversial issue whether multiple languages are represented in common or distinct cerebral areas. Seven direct brain mapping studies from different teams focused on bilingualism and multilingualism. All these studies showed that even if cerebral representation of language in multilingual patients could be grossly located in the same cortical region, it was possible to individualise distinct language-specific areas by direct cortical stimulation in the dominant frontal and temporo-parietal regions. Task- and language-specific sites were also described, demonstrating an important specialisation of some cortical areas. Using subcortical stimulation, some authors were able to find specific white matter tracts for different languages. Finally, all authors recommend in bilingual patients who need brain mapping for neurosurgical purpose to test all languages in which the subjects are fluent.