Philippe Major

Philippe Major
Université de Montréal | UdeM · Department of Neurosciences

MD

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81
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Publications

Publications (81)
Article
Objective This study aims to develop and internally validate a clinical risk score to predict incident renal angiomyolipoma (AML) and pulmonary lymphangioleiomyomatosis (LAM) in people with tuberous sclerosis complex (TSC). Study design Data from 2420 participants in the TSC Alliance Natural History Database were leveraged for these analyses. Logi...
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Introduction Pediatric frontal and temporal lobe epilepsies (FLE, TLE) have been associated with language impairments and structural and functional brain alterations. However, there is no clear consensus regarding the specific patterns of cerebral reorganization of language networks in these patients. The current study aims at characterizing the ce...
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Objective This longitudinal cohort study aimed to identify trajectories of parent well‐being over the first 2 years after their child's evaluation for candidacy for epilepsy surgery, and to identify the baseline clinical and demographic characteristics associated with these trajectories. Parent well‐being was based on parent depressive and anxiety...
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Background Epilepsy is the most common paediatric neurological disorder. An estimated 4% of the general population will have an unprovoked epileptic seizure at least once in their lifetime. Of these, about 40% will experience a recurrence within two years. The International League Against Epilepsy (ILAE) established that one part of the definition...
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Purpose: Seizure freedom is an important predictor of health-related quality of life (HRQOL) after pediatric epilepsy surgery. This study aimed to identify the pre-operative predictors of HRQOL 2 years after epilepsy surgery in children with drug-resistant epilepsy. Methods: This multicenter prospective cohort study assessed pre-operative predic...
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Objectives The purpose of this longitudinal cohort study was to examine the variables that influence health‐related quality of life (HRQOL) after epilepsy surgery in children. We examined whether treatment type (surgical vs medical therapy) and seizure control are related to other variables that have been shown to influence HRQOL, namely depressive...
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Importance: Health-related quality of life (HRQOL) is regarded as a key outcome for evaluating treatment efficacy. However, it is uncertain how HRQOL evolves after epilepsy surgery compared with medical therapy, such as whether it continues to improve over time, improves and then remains stable, or deteriorates after a period of time. Objective:...
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Aim: To evaluate clinicians' and patients' perceptions of pharmacogenetic testing in a clinical setting. Materials & methods: This is a pragmatic mixed-method prospective observational study. Hospital pharmacists and neurologists participated in focus groups regarding pharmacogenetic testing; patients who received pharmacogenetic testing and their...
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We present five cases of pediatric drug-resistant epilepsy (DRE) that failed management using high cannabidiol (CBD) doses, but had significant reduction in seizure frequency with reintroduction or increasing doses of tetrahydrocannabinol (THC). There is growing evidence supporting the use of whole-plant CBD-rich extracts (containing THC and other...
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This study investigated which specific behavioural issues is best associated with adaptive functioning in three specific genetic syndromes. Behavioural issues were assessed in neurotypical (NT) (n = 43), Tuberous sclerosis complex (TSC) (n = 19), Down syndrome (DS) (n = 24) and Fragile X syndrome (FXS) (n = 23) participants ranging from 3 to 30 yea...
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Objective To examine longitudinal changes and predictors of depression and anxiety 2 years following resective epilepsy surgery, compared to no surgery, in children with drug-resistant epilepsy (DRE). Method This multicenter cohort study involved 128 children and adolescents with DRE (48 surgical, 80 nonsurgical; 8–18 years) who completed self-rep...
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Background: Disease severity is tremendously variable in tuberous sclerosis complex (TSC). In contrast with the detailed guidelines available for TSC diagnosis and management, clinical practice lacks adequate tools to evaluate the prognosis, especially in the case of in utero diagnosis. In addition, the correlation between genotypes and phenotypes...
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Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed a cross-sectional pilot study including 55 parents from 36 families to assess the level of stress experienced by parents of patients with genetically determined leukoenc...
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A 2-year-old Caucasian boy with tuberous sclerosis complex presented to the emergency department with lethargy and new onset myoclonias. Pancreatitis, thrombocytopenia, and coagulopathy associated to a decreased level of consciousness were diagnosed. Valproic acid had been initiated 13 months before and had been slowly increased to a dose of approx...
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Résumé Objectif Décrire la démarche de mise à niveau de l’offre de soins pharmaceutiques en neurologie en ciblant l’épilepsie. Méthodologie Étude descriptive composée d’une revue de la littérature traitant des rôles et des impacts du pharmacien dans la prise en charge de l’épilepsie, d’une description de l’organisation des soins entourant les pat...
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Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study. Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escal...
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BACKGROUND Infants with childhood-onset epilepsies, including epileptic encephalopathies, are at high risk of developmental challenges such as motor and language delays. There has been a growing focus on developmental screening instruments due to the association between delayed development and long-term adverse outcomes, including negative impacts...
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Background Fragile X syndrome (FXS) is a neurodevelopmental genetic disorder causing cognitive and behavioural deficits. Repetition suppression (RS), a learning phenomenon in which stimulus repetitions result in diminished brain activity, has been found to be impaired in FXS. Alterations in RS have been associated with behavioural problems in FXS;...
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Infantile spasms (IS) is a catastrophic epilepsy where treatment precocity improves outcome. Previous studies demonstrated an association between asymmetric hypsarrhythmia on EEG and ipsilateral hemispheric lesions on MRI, suggesting a possible role of cortical lesions in the initiation of IS. Epileptiform abnormalities appearing during early infan...
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Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We performed whole-genome sequenci...
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Purpose Rolandic epilepsy (RE), also called benign epilepsy with centrotemporal spikes (BECTS) is the most common childhood epilepsy syndrome. RE is associated with cognitive difficulties, which can affect children's quality of life. The underlying causes of these cognitive impairments are unclear. The objective of this prospective study is to inve...
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Background: We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. Methods: Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research cohorts, as well as from 43 patients from the liter...
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Purpose: Seizures are common in critically ill neonates. Both seizures and antiepileptic treatments may lead to short term complications and worsen the outcomes. Predicting the risks of seizure reoccurrence could enable individual treatment regimens and better outcomes. We aimed to identify EEG signatures of seizure reoccurrence by investigating p...
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Fragile X Syndrome (FXS) is a neurodevelopmental genetic disorder associated with cognitive and behavioural deficits. In particular, neuronal habituation processes have been shown to be altered in FXS patients. Yet, while such deficits have been primarily explored using auditory stimuli, less is known in the visual modality. Here, we investigated t...
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Tuberous sclerosis complex is associated with benign tumors such as cardiac rhabdomyomas (RHM) caused by the disinhibition of the mammalian target of rapamycin (mTOR) protein. Recent reports on everolimus, an mTOR inhibitor, have shown size reduction of RHM. We compared cases recently treated with everolimus to historic controls whose first echocar...
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Seizures are common and worsen the outcome in critically ill neonates. Predicting seizure recurrence could allow individualizing antiepileptic treatment and improving the outcome. To identify EEG signatures of seizure recurrence, we investigated periictal spectral power and electrographic characteristics of seizures in five consecutive asphyxiated...
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Background: Sturge-Weber syndrome is characterized by a facial port-wine stain associated with either or both a retinal angioma and a cerebral pial angioma. Because a pial angioma may not be evident on the initial imaging studies, individuals at risk for epilepsy are often not identified before their first seizure. The aim of this study is to iden...
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p> Introduction: Optimal clinical assessment and subsequent followup of patients with or suspected of having a hereditary renal cell carcinoma syndrome (hRCC) is not standardized and practice varies widely. We propose protocols to optimize these processes in patients with hRCC to encourage a more uniform approach to management that can then be eval...
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Sturge Weber Syndrome (SWS) patients at risk of epilepsy are often not identified before their first seizure which leads to unnecessary follow up of many patients with facial angioma. Methods: The medical photography database of our institution has been reviewed to identify SWS patients followed between 1993 and 2013. Patients with isolated glaucom...
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Planning for neurology training necessitated a reflection on the experience of graduates. We explored practice characteristics, and training experience of recent graduates. Methods: Graduates from 2010-2014 completed a survey. Results: Response rate was 37% of 211. 56% were female. 91% were adult neurologists. 65% practiced in an outpatient setting...
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Background Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can present with many disabling neurological disorders, the most common being epilepsy. Although it is a chronic multi-system disease, healthcare utilization and long-term outcome of subjects with TSC are not yet well defined. The goal of this study was to evaluate the di...
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Background: Little knowledge exists on the availability of academic and community paediatric neurology positions. This knowledge is crucial for making workforce decisions. Our study aimed to: 1) obtain information regarding the availability of positions for paediatric neurologists in academic centres; 2) survey paediatric neurology trainees regard...
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Fatty acid oxidation disorders and lipin-1 deficiency are the commonest genetic causes of rhabdomyolysis in children. We describe a lipin-1-deficient boy with recurrent, severe rhabdomyolytic episodes from the age of 4years. Analysis of the LPIN1 gene that encodes lipin-1 revealed a novel homozygous frameshift mutation in exon 9, c.1381delC (p.Leu4...
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Aim: Lacosamide is an antiepileptic drug approved for the treatment of focal epilepsy in adult patients. The aim of this observational study was to review our centre's experience with lacosamide and to characterize its effectiveness and tolerability as an adjunctive antiepileptic drug in a retrospective cohort of children with refractory focal epi...
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Introduction: Children with benign epilepsy with centro-temporal spikes (BECTS) often have language problems. Abnormal epileptic activity is found in central and temporal brain regions, which are involved in reading and semantic and syntactic comprehension. Using functional magnetic resonance imaging (fMRI), we examined reading networks in BECTS c...
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Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can present with many disabling neurological symptoms, the most common being seizures. Although it is a chronic systemic syndrome, healthcare utilization and long-term outcome of subjects with TSC are not well defined. The goal of this study was to evaluate the direct cost and long-...
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Debate persists in Canada about the cost and benefit of vagal nerve stimulation in patients with refractory epilepsy. The aim of our study was to evaluate the impact of a vagal nerve stimulator on the seizure frequency and the admission rate of children with refractory epilepsies over five years of follow-up. Methods: 52 patients were implanted bet...
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Lymphangioleiomyomatosis (LAM) is a manifestation of Tuberous Sclerosis Complex (TSC) that causes destruction of the lung and chronic respiratory failure. Population-based estimates of demographics, clinical outcomes, and health care utilization are lacking for TSC and LAM. Data on demographics, clinical outcomes, and health care utilization in the...
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Background: Tuberous sclerosis complex is characterized by the growth of benign tumors in multiple organs, caused by the disinhibition of the mammalian target of rapamycin (mTOR) protein. mTOR inhibitors, such as everolimus, are used in patients with tuberous sclerosis complex, mainly to reduce the size of renal angiomyolipomas and subependymal gi...
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Rhabdomyoma (RHM) is a benign cardiac tumour usually associated with tuberous sclerosis complex (TSC). Most RHMs are asymptomatic and regress spontaneously during the first years of life. Haemodynamically significant RHMs are classically treated with surgical excision. We present a case of a premature infant, born to a mother having TSC, with a pre...
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Background Fragile X Syndrome (FXS) is the most common monogenic form of intellectual disability and one of the few known monogenic causes of autism. It is caused by a trinucleotide repeat expansion in the FMR1 (‘Fragile X Mental Retardation 1’) gene, which prevents expression of the ‘Fragile X Mental Retardation Protein’ (FMRP). In FXS, the absenc...
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Background Infantile spasms (IS) is an early-onset epileptic encephalopathy of unknown etiology in approximately 40% of patients. We hypothesised that unexplained IS cases represent a large collection of rare single-gene disorders.Methods We investigated 44 children with unexplained IS using comparative genomic hybridisation arrays (aCGH) (n=44) fo...
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A 14-year-old girl presented with a prolonged migraine visual aura of several weeks' duration. Symptoms gradually resolved over a 6-week period, with no recurrence of visual aura over a 20-month follow-up period. Although there is significant overlap between the features of stereotypical and persistent migraine auras, or "visual snow," the latter t...
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Background: Mutations in TSC1 or TSC2 cause the tuberous sclerosis complex (TSC), a disorder characterised by the development of hamartomas or benign tumours in various organs as well as the variable presence of epilepsy, intellectual disability (ID) and autism. TSC1, TSC2 and the recently described protein TBC1D7 form a complex that inhibits mTOR...
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We present two methods of implantation for the investigation of suspected insular and perisylvian epilepsy that combine depth and subdural electrodes to capitalize on the advantages of each technique. Retrospective study of all intracranial EEG studies that included insular electrodes from 2004-2010. Patients were divided according to the implantat...
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The purpose of this study was to assess the prevalence of and to identify epidemiologic, genetic, electrophysiologic, and neuroanatomic risk factors for autism spectrum disorders (ASD) in a cohort of patients with tuberous sclerosis complex (TSC). A total of 103 patients with TSC were evaluated for ASD. A retrospective review of patients' records w...
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Rapamycin inhibits the mTOR (target of rapamycin) pathway and extends lifespan in multiple species. The tuberous sclerosis complex (TSC) protein is a negative regulator of mTOR. In humans, loss of the TSC protein results in a disorder characterized clinically by the growth of benign tumors in multiple organs, due to overactivation of mTOR inhibitio...
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The phenotypic and etiologic spectrum in adults with nodular heterotopias (NHs) has been well characterized. However, there are no large pediatric case series. We, therefore, wanted to review the clinical features of NHs in our population. Hospital records of 31 patients with pathology or imaging-confirmed NHs were reviewed. Two-sided Fisher's exac...
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Tuberous sclerosis complex (TSC) is associated with the potential development of benign hamartomas, including subependymal giant cell astrocytomas (SEGAs). Intracranial hypertension can be caused by SEGAs due to their propensity to block the foramen of Monro. The traditional management approach is to monitor SEGAs with periodic neuroimaging and to...
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Although epilepsy affects most patients with tuberous sclerosis complex (TSC), little is known about the natural history of epilepsy in this genetic disease. A retrospective chart review of all patients with TSC seen between January 2002 and October 2008. Charts were reviewed for a history of infantile spasms (IS), seizure other than IS, refractory...
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Nearly 90% of patients with tuberous sclerosis complex (TSC) develop epilepsy; however the mechanisms of epileptogenesis remain unclear. Some cortical tubers are thought to be epileptogenic while others are not. This study aimed to evaluate whether tuber burden, size or type seen on magnetic resonance imaging (MRI) co-registers with interictal epil...
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Tuberous sclerosis complex (TSC) is a genetic condition characterized by the presence of hamartomatous lesions in multiple organs, including tubers in the brain. The majority of patients with TSC have epilepsy. Some cortical tubers are epileptic foci, while others appear to be physiologically quiescent. It is unknown whether variations in tuber mor...
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Ischemic cerebral vascular accidents (CVAs) in children result in epilepsy in 25% of patients, which is refractory in 7% of cases. Repeated seizures worsen the global and cognitive prognosis of these patients. To evaluate the prognosis of epilepsy and cognitive development in children with refractory seizures following a CVA, the authors retrospect...
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The purpose of this study was to characterize the epileptogenicity of tubers and surrounding cortex in patients with tuberous sclerosis complex (TSC). Three pediatric patients with TSC and intractable epilepsy underwent surgical resection of tubers associated with epileptogenic foci. In all patients, presurgical imaging revealed a prominent tuber t...
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Behavioral side effects related to the use of levetiracetam (LEV) in epilepsy are increasingly being recognized. Patients followed in our center have reported improvement of these side effects after starting pyridoxine (vitamin B(6)) supplements. Using mailed questionnaires, retrospective chart reviews, and phone call follow-ups, we analyzed 42 ped...
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Self-injurious behavior (SIB) has been observed in people with tuberous sclerosis complex (TSC), although the frequency of SIB in TSC is largely unknown. SIB is associated with intellectual and developmental disabilities, but there is no single cause of SIB. We retrospectively examined the frequency of SIB in a population of 257 patients with TSC a...
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The aim of the study described here was to characterize the efficacy and safety of vagus nerve stimulation in a population of patients with tuberous sclerosis complex (TSC) and intractable epilepsy. This retrospective study comprised 16 patients with TSC who underwent implantation of a vagus nerve stimulator for treatment of intractable epilepsy. T...
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To review the efficacy, cognitive outcome and safety profile in children treated with vigabatrin (VGB) for infantile spasms (IS) and partial epilepsies related to tuberous sclerosis complex (TSC) and other etiologies. Retrospective review of children followed in the Pediatric Epilepsy Program of Massachusetts General Hospital for Children between M...
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This study defines the clinical characteristics and evolution of 16 epileptic children with hippocampal asymmetry (HA) without sclerosis on MRI. The association of a positive family history of epilepsy (11/16), low incidence of febrile seizures (2/16), and benign prognosis (seizure control in monotherapy in 11/16, mean follow-up = 4.3 years, range...
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To establish the incidence of abnormalities in the expression of retinoic acid receptor-beta (RARbeta) in bronchial cells and determine the capacity of 13-cis-retinoic acid (13-CRA) to correct such abnormalities. One hundred eighty-eight smokers had a medical indication for bronchoscopy and were studied with bronchial brushings. Bronchial brushing...

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