Publications by authors named "Christine Saint-Martin"

59 Publications

MNI SISCOM: an Open-Source Tool for Computing Subtraction Ictal Single-Photon Emission CT Coregistered to MRI.

J Digit Imaging 2021 Feb 18. Epub 2021 Feb 18.

Department of Paediatric Surgery, Division of Neurosurgery, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada.

Subtraction ictal single-photon emission computed tomography (SPECT) coregistered to MRI (SISCOM) is a well-established technique for quantitative analysis of ictal vs interictal SPECT images that can contribute to the identification of the seizure onset zone in patients with drug-resistant epilepsy. However, there is presently a lack of user-friendly free and open-source software to compute SISCOM results from raw SPECT and MRI images. We aimed to develop a simple graphical desktop application for computing SISCOM. MNI SISCOM is a new free and open-source software application for computing SISCOM and producing practical MRI/SPECT/SISCOM image panels for review and reporting. The graphical interface allows any user to quickly and easily obtain SISCOM images with minimal user interaction. Additionally, MNI SISCOM provides command line and Python interfaces for users who would like to integrate these features into their own scripts and pipelines. MNI SISCOM is freely available for download from: https://github.com/jeremymoreau/mnisiscom .
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http://dx.doi.org/10.1007/s10278-021-00422-9DOI Listing
February 2021

Isolated bilateral congenital lacrimal gland agenesis-a case series.

J AAPOS 2021 Feb 16. Epub 2021 Feb 16.

Department of Ophthalmology & Visual Sciences, McGill University, Montreal, Quebec, Canada.

We report 2 pediatric cases of isolated bilateral congenital lacrimal gland agenesis (CLGA). Patient 1 (1 year of age) and patient 2 (2 years of age) presented with symptoms of alacrimia and were diagnosed with bilateral isolated CLGA based on magnetic resonance imaging. Both patients were otherwise healthy, with no systemic associations. Molecular analysis for genetic causes of CLGA were negative. Both have been successfully medically managed.
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http://dx.doi.org/10.1016/j.jaapos.2020.11.008DOI Listing
February 2021

Prosopagnosia seizure semiology in a 10-year-old boy: a functional neuroimaging study.

BMJ Case Rep 2020 Dec 22;13(12). Epub 2020 Dec 22.

Department of Pediatric Surgery, Neurosurgery Division, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada

We illustrate a case of post-traumatic recurrent transient prosopagnosia in a paediatric patient with a right posterior inferior temporal gyrus haemorrhage seen on imaging and interictal electroencephalogram abnormalities in the right posterior quadrant. Face recognition area mapping with magnetoencephalography (MEG) and functional MRI (fMRI) was performed to clarify the relationship between the lesion and his prosopagnosia, which showed activation of the right fusiform gyrus that colocalised with the lesion. Lesions adjacent to the right fusiform gyrus can result in seizures presenting as transient prosopagnosia. MEG and fMRI can help to attribute this unique semiology to the lesion.
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http://dx.doi.org/10.1136/bcr-2020-237228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757463PMC
December 2020

The utility of arterial spin labeling in the presurgical evaluation of poorly defined focal epilepsy in children.

J Neurosurg Pediatr 2020 Dec 25:1-10. Epub 2020 Dec 25.

4Pediatric Neurosurgery.

Objective: The authors sought to assess the utility of arterial spin labeling (ASL) perfusion 3T-MRI for the presurgical evaluation of poorly defined focal epilepsy in pediatric patients.

Methods: Pseudocontinuous ASL perfusion 3T-MRI was performed in 25 consecutive children with poorly defined focal epilepsy. ASL perfusion abnormalities were detected qualitatively by visual inspection and quantitatively by calculating asymmetry index (AI) maps and significant z-score cluster maps based on successfully operated cases. ASL results were prospectively compared to scalp EEG, structural 3T-MRI, FDG-PET, ictal/interictal SPECT, magnetoencephalography (MEG), and intracranial recording results, as well as the final surgically proven epileptogenic zone (EZ) in operated patients who had at least 1 year of good (Engel class I/II) seizure outcome and positive histopathology results.

Results: Qualitative ASL perfusion abnormalities were found in 17/25 cases (68%), specifically in 17/20 MRI-positive cases (85.0%) and in none of the 5 MRI-negative cases. ASL was concordant with localizing scalp EEG findings in 66.7%, structural 3T-MRI in 90%, FDG-PET in 75%, ictal/interictal SPECT in 62.5%, and MEG in 75% of cases, and with intracranial recording results in 40% of cases. Eleven patients underwent surgery; in all 11 cases the EZ was surgically proven by positive histopathology results and the patient having at least 1 year of good seizure outcome. ASL results were concordant with this final surgically proven EZ in 10/11 cases (sensitivity 91%, specificity 50%). All 10 ASL-positive patients who underwent surgery had positive surgical pathology results and good long-term postsurgical seizure outcome at a mean follow-up of 39 months. Retrospective quantitative analysis based on significant z-score clusters found 1 true-positive result that was missed by qualitative analysis and 3 additional false-positive results (sensitivity 100%, specificity 23%).

Conclusions: ASL supports the hypothesis regarding the EZ in poorly defined focal epilepsy cases in children. Due to its convenience and noninvasive nature, the authors recommend that ASL be added routinely to the presurgical MRI evaluation of epilepsy. Future optimized quantitative methods may improve the diagnostic yield of this technique.
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http://dx.doi.org/10.3171/2020.7.PEDS20397DOI Listing
December 2020

Spontaneous Multilevel Cerebrospinal Fluid Leak in Marfan Syndrome.

Ann Neurol 2020 10 14;88(4):855-856. Epub 2020 Jul 14.

Department of Pediatrics, Division of Child Neurology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.

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http://dx.doi.org/10.1002/ana.25837DOI Listing
October 2020

Teaching Video NeuroImages: Pathologic yawning: A sign of brainstem involvement in acute disseminated encephalomyelitis?

Neurology 2020 06 4;94(23):e2497-e2498. Epub 2020 May 4.

From the Department of Pediatrics (V.B., K.A.M.), Division of Child Neurology, and Department of Medical Imaging (C.S.-M.), Montreal Children's Hospital; Department of Neurology & Neurosurgery (K.A.M.), and Research Institute of the McGill University Health Centre (K.A.M.), McGill University Health Centre, Montreal, Canada.

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http://dx.doi.org/10.1212/WNL.0000000000009595DOI Listing
June 2020

X-Linked Familial Focal Epilepsy Associated With Xp22.31 Deletion.

Pediatr Neurol 2020 07 13;108:113-116. Epub 2020 Apr 13.

Department of Medical Imaging, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.

Background: The genetic basis for familial focal epilepsy is poorly understood, with most of the known genetic causes occurring via autosomal dominant inheritance. X-linked familial focal epilepsy has not been previously reported.

Methods: We reviewed our research database for cases of X-linked focal epilepsy.

Results: We identified three boys with X-linked ichthyosis and focal epilepsy, including two maternal cousins. Age of seizure onset ranged from seven to 10 years, and all three patients had seizures that were relatively easily controlled. The epilepsy phenotype in all boys was consistent with self-limited focal epilepsy of childhood, most closely resembling childhood epilepsy with centrotemporal spikes. Brain magnetic resonance imaging was normal in two of the boys, with a third found to have a suspected focal cortical dysplasia. All three boys carried maternally inherited hemizygous Xp22.31 deletions (estimated size 0.9 to 1.66 Mb), affecting four to six genes. Of the affected genes, only STS has clear clinical relevance; deletions, and pathogenic variants in STS cause X-linked ichthyosis, although all patients described had only minor skin findings.

Conclusions: The findings in these patients illustrate that X-linked familial focal epilepsy can occur, although it is a rare entity. Although STS pathogenic variants are likely better categorized as an epilepsy risk factor, variants in this gene may partially explain the male predominance observed in specific epilepsy phenotypes, namely childhood epilepsy with centrotemporal spikes.
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http://dx.doi.org/10.1016/j.pediatrneurol.2020.02.008DOI Listing
July 2020

Eight-Year Experience With 3-T Intraoperative MRI Integration in Focal Pediatric Epilepsy Surgery: Impact on Extent of Resection, Residual Volumes, and Seizure Outcomes.

AJR Am J Roentgenol 2020 06 24;214(6):1343-1351. Epub 2020 Mar 24.

Department of Diagnostic Imaging, Montreal Children's Hospital, McGill University, 1001 Decarie Blvd, Rm B02.7005, Montreal, QC H4A 3J1, Canada.

The purpose of this study was to investigate the influence of 3-T intraoperative MRI (ioMRI) on the extent of resection of pediatric focal epileptogenic lesions, residual lesion volumes, and postoperative seizure outcomes. All surgical procedures for focal epilepsy from 2003 to 2017 were retrospectively reviewed. Patients were divided into two groups: those who underwent ioMRI and those who did not. Each group was subdivided into two subcategories according to preoperative MRI visualization of the lesion: those with well-defined and those with poorly defined lesions. The volumes of preoperative lesions and postoperative residual lesions were delineated. Outcome data and patient characteristics were reviewed. The results were compared between the two groups and the two subcategories. Eighty patients were included: 45 in the ioMRI group (24 with well-defined lesions, 21 with poorly defined lesions) and 35 in the non-ioMRI group (18 with well-defined lesions, 17 with poorly defined lesions). The well-defined lesions included tumors and vascular lesions. The poorly defined lesions included malformations of cortical development, hippocampal sclerosis, and tuberous sclerosis. The mean follow-up duration was 5.1 ± 3.3 years. The rate of gross total resection was not significantly different between the ioMRI and non-ioMRI groups ( 0.46). However, ioMRI findings facilitated further resection during surgery, increasing gross total resection by an additional 11.1%. The ioMRI group had a significant reduction in percentage of residual volume ( < 0.001). Outcome data suggested that ioMRI is protective against poor Engel score ( = 0.048). Although ioMRI prolonged the mean operative time by 1.2 hours ( = 0.002), the additional time was not associated with additional complications. Integration of ioMRI into focal epilepsy surgery was associated with smaller residual lesions and was protective against poor Engel score. It prolonged the operative time but without increasing the number of complications.
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http://dx.doi.org/10.2214/AJR.19.22336DOI Listing
June 2020

Correction to: Efficacy of Dabrafenib for three children with brainstem BRAF positive ganglioglioma.

J Neurooncol 2019 Dec;145(3):595

Department of Pediatrics, Centre Mère-enfant Soleil du CHU de Québec-Université Laval, Québec, Canada.

In the original article, the author names were published incorrectly. The names are correct in this publication.
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http://dx.doi.org/10.1007/s11060-019-03350-5DOI Listing
December 2019

Lateral Medullary Syndrome Due to Left Vertebral Artery Occlusion in a Boy Postflexion Neck Injury.

Child Neurol Open 2019 6;6:2329048X19867800. Epub 2019 Aug 6.

Division of Pediatric Neurology, Departments of Pediatrics & Neurology/Neurosurgery, The Montreal Children's Hospital, McGill University, Montreal, Québec, Canada.

Lateral medullary syndrome is rare in pediatrics. It is characterized by neurological deficits due to an ischemic lesion in the lateral medulla. The authors describe a 17-year-old boy who developed lateral medullary syndrome in the context of a hyperflexion neck injury while diving in shallow water with traumatic vascular injury. He had "crossed" neurological deficits above and below the neck. His magnetic resonance angiography showed intra- and extracranial left vertebral artery occlusion and his magnetic resonance imaging showed signal abnormality involving the left lateral medulla and inferomedial cerebellum in keeping with an infarct secondary to left vertebral artery and left posterior inferior cerebellar artery occlusion. Good neurological recovery was observed on heparin therapy started after surgical treatment of traumatic injury. To our knowledge, this is the first reported case of lateral medullary syndrome in a pediatric population related to a flexion neck injury. The authors emphasize the importance of a high level of suspicion for accurate diagnosis.
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http://dx.doi.org/10.1177/2329048X19867800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852355PMC
August 2019

Quantification of apparent axon density and orientation dispersion in the white matter of youth born with congenital heart disease.

Neuroimage 2020 01 9;205:116255. Epub 2019 Oct 9.

Advances in Brain & Child Development (ABCD) Research Laboratory, Research Institute of the McGill University Health Centre, Montreal, QC, Canada; Department of Neurology & Neurosurgery, Faculty of Medicine, McGill University, Montreal, QC, Canada; School of Physical & Occupational Therapy, McGill University, Montreal, QC, Canada; Department of Pediatrics, Division of Neonatology, Montreal Children's Hospital, Montreal, QC, Canada. Electronic address:

Background: White matter alterations have previously been demonstrated in adolescents born with congenital heart disease (CHD) using diffusion tensor imaging (DTI). However, due to the non-specific nature of DTI metrics, it is difficult to interpret these findings in terms of their microstructural implications. This study investigated the use of neurite orientation dispersion and density imaging (NODDI), which involves the acquisition of advanced multiple b-value data over two shells and provides proxy measures of apparent axon density and orientation dispersion within white matter, as a complement to classic DTI measures.

Study Design: Youth aged 16 to 24 years born with complex CHD and healthy peers underwent brain magnetic resonance imaging. White matter tract volumes and tract-average values of DTI and NODDI metrics were compared between groups. Tract-average DTI and NODDI results were spatially confirmed using tract-based spatial statistics.

Results: There were widespread regions of lower tract-average neurite density index (NDI) in the CHD group as compared to the control group, particularly within long association tracts and in regions of the corpus callosum, accompanied by smaller white matter tract volumes and isolated clusters of lower fractional anisotropy (FA). There were no significant differences in orientation dispersion index (ODI) between groups.

Conclusion: Lower apparent density of axonal packing, but not altered axonal orientation, is a key microstructural factor in the white matter abnormalities observed in youth born with CHD. These impairments in axonal packing may be an enduring consequence of early life brain injury and dysmaturation and may explain some of the long-term neuropsychological difficulties experienced by this at-risk group.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116255DOI Listing
January 2020

The Feasibility of Fast MRI to Reduce CT Radiation Exposure With Acute Traumatic Head Injuries.

Pediatrics 2019 10;144(4)

Division of Pediatric Medical Imaging, Department of Diagnostic Radiology, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.

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http://dx.doi.org/10.1542/peds.2019-2387DOI Listing
October 2019

Efficacy of Dabrafenib for three children with brainstem BRAF positive ganglioglioma.

J Neurooncol 2019 Oct 9;145(1):135-141. Epub 2019 Sep 9.

Department of Pediatrics, Centre Mère-enfant Soleil du CHU de Québec-Université Laval, Québec, Canada.

Purpose: Children with unresectable brainstem-infiltrated ganglioglioma have poor progression-free survival when treated with conventional chemotherapy and radiation regimens. The BRAF mutation occurs in a large number of gangliogliomas, making them amenable for targeted therapy using mutation-specific kinase inhibitors. However, limited data exists on the effectiveness and best treatment duration of these inhibitors in this tumor setting.

Method: Retrospective description of three cases of childhood brainstem ganglioglioma with BRAF mutation treated in the long-term with Dabrafenib, a specific BRAF kinase inhibitor.

Results: Dabrafenib resulted in rapid tumoral regression and significant and durable clinical and radiological improvement. However, all patients had rapid clinical and radiological relapse within days to weeks following treatment discontinuation but showed similar rapid and sustained therapeutic response when Dabrafenib was re-introduced. This targeted therapy has been well tolerated despite its long-term use of 4.8 to 5.5 years in the three patients.

Conclusion: Dabrafenib is effective and seemingly safe and well tolerated in our three patients. We observed sustained chemosensitivity even when re-introducing this kinase inhibitor after its discontinuation after 2 years of therapy. These cases indicate the need to re-evaluate the timing and means of Dabrafenib discontinuation in pediatric patients with BRAF mutated gangliogliomas and better assess the future implications of its long-term use.
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http://dx.doi.org/10.1007/s11060-019-03280-2DOI Listing
October 2019

A new imaging entity consistent with partial ectopic posterior pituitary gland: report of six cases.

Pediatr Radiol 2020 01 30;50(1):107-115. Epub 2019 Aug 30.

Department of Radiology, McGill University Health Centre, 1001 Decarie Blvd., Room B02.7006, Montreal, QC, H4A 3J1, Canada.

Background: Abnormal posterior pituitary development including ectopic location has been associated with endocrine manifestations of anterior pituitary dysfunction.

Objective: We describe an unreported clinical and radiologic entity we call partial ectopic posterior pituitary for which associated endocrine consequences are not known.

Materials And Methods: We selected pediatric head MRI examinations from 2005 to 2017 based on the finding of a double midline sellar and suprasellar bright spot on T1-weighted sequence. Medical history, physical examination, pituitary hormonal profile and bone age evaluation were extracted from the medical record of the selected patients. An experienced pediatric neuroradiologist reviewed head MRIs, which were performed on 3-tesla (T) magnet and included at least sagittal T1-weighted imaging centered on the sella turcica obtained with and without fat suppression.

Results: In six cases, two midline bright spots were identified on T1-weighted sequences obtained both with and without fat suppression. While one spot was located at the expected site of the neurohypophysis in the posterior sella, the second one was in the region of the median eminence, suggesting partial ectopic posterior pituitary gland. Growth hormone deficiency, either isolated (n=1) or combined with thyroid stimulating hormone deficiency (n=1) was found. None of the children had clinical signs of posterior pituitary dysfunction.

Conclusion: We describe an unreported imaging entity suggesting partial ectopic posterior pituitary gland in six children. Anterior pituitary hormone deficiencies might be detected in those children and long-term follow-up could provide additional information on the development of other pituitary hormone deficiencies.
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http://dx.doi.org/10.1007/s00247-019-04502-5DOI Listing
January 2020

Maternally inherited MAF variant associated with variable expression of Aymé-Gripp syndrome.

Am J Med Genet A 2019 11 7;179(11):2233-2236. Epub 2019 Aug 7.

Department of Medical Genetics, McGill University Health Centre, Montreal, Quebec, Canada.

Aymé-Gripp syndrome is an intellectual disability syndrome characterized by autism spectrum disorder, cataracts, sensorineural hearing loss, skeletal involvement, seizures, cardiac anomalies, and distinctive facial features. The condition is caused by pathogenic variants in MAF. To date, less than 20 cases have been reported, the majority having de novo mutations. Here, we report a patient with classical features of Aymé-Gripp syndrome who inherited a MAF variant, c.206C>G (p.P69R), from a mother with normal intellectual function and normal hearing but with cataract and significant proteinuria. To the best of our knowledge, this is the first report of a patient who inherited a MAF causative variant from a parent with normal intellect. Although the syndrome typically has multiple malformations and intellectual disability, we suggest that a mild phenotype could exist. In addition, we suggest that the basal ganglia calcifications present in our proband could be a novel finding associated with MAF variants and offer further support for the relationship between these variants and late manifestations of renal disease.
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http://dx.doi.org/10.1002/ajmg.a.61299DOI Listing
November 2019

Hyperacute Infarct on Intraoperative Diffusion Imaging of Pediatric Brain Tumor Surgery.

Can J Neurol Sci 2019 09 29;46(5):550-558. Epub 2019 Jul 29.

Division of Neurosurgery, Department of Pediatric Surgery, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada.

Background: Brain neoplasms are the second-most prevalent cancer of childhood for which surgical resection remains the main treatment. Intraoperative MRI is a useful tool to optimize brain tumor resection. It is, however, not known whether intraoperative MRI can detect complications such as hyperacute ischemic infarcts.

Methods: A retrospective analysis of pre- and intraoperative MRIs including DWI sequence and correlation with early and 3-month postoperative MRIs was conducted to evaluate the incidence of hyperacute arterial infarct during pediatric brain tumor resection. Patient demographics, pathological type, tumor location, resection type as well as preoperative tumoral vessel encasement, evolution of the area of restricted diffusion were collected and analyzed comparatively between the group with acute infarct and the control group. Extent of the hyperacute infarct was compared to both early postsurgical and 3-month follow-up MRIs.

Results: Of the 115 cases, 13 (11%) developed a hyperacute arterial ischemic infarct during brain tumor resection. Tumoral encasement of vessels was more frequent in the infarct group (69%) compared to 25.5% in the control group. Four cases showed additional vessel irregularities on intraoperative MRI. On early follow-up, the infarcted brain area had further progressed in six cases and was stable in seven cases. No further progression was noted after the first week post-surgery.

Conclusions: Hyperacute infarcts are not rare events to complicate pediatric brain tumor resection. Tumoral encasement of the circle of Willis vessels appears to be the main risk factor. Intraoperative DWI underestimates the final extent of infarcted tissue compared to early postsurgical MRI.
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http://dx.doi.org/10.1017/cjn.2019.226DOI Listing
September 2019

High-Frequency Ultrasound: A Novel Diagnostic Tool to Measure Pediatric Tonsils in 3 Dimensions.

Otolaryngol Head Neck Surg 2019 11 14;161(5):856-861. Epub 2019 May 14.

Department of Pediatric Otolaryngology-Head and Neck Surgery, Montreal Children's Hospital, Montreal, Quebec, Canada.

Objective: A wide variety of pathologies can affect the palatine tonsils. Ultrasound is a commonly used modality for assessing head and neck masses in children; however, its use in tonsillar evaluation has not been widely explored. The objective of this study was to measure 3-dimensional tonsillar size with ultrasound, in centimeters, and correlate these measurements with actual ex vivo dimensions on pathology specimens.

Study Design: We performed a prospective cohort study.

Setting: The study was set in a tertiary care children's hospital.

Subjects And Methods: Children undergoing tonsillectomy were included in the study. Transcervical high-frequency ultrasonography (HFU) was performed prior to surgery to obtain 3-dimensional measurements of the right and left palatine tonsils. Mean sizes were compared to ex vivo tonsil measurements and correlations were obtained.

Results: Seventy-five consecutive children underwent a transcervical HFU, with a total of 150 tonsils analyzed. The mean differences between HFU and pathology measurements were -0.08 cm and -0.24 cm for the right and left craniocaudal axes, -0.19 cm and -0.18 cm for the right and left mediolateral axes, and 0.05 cm and 0.03 cm for the right and left anteroposterior axes. Correlation coefficients between ultrasound and pathology measurements were all above 0.5.

Conclusion: HFU can accurately measure the size of pediatric tonsils in 3 dimensions.
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http://dx.doi.org/10.1177/0194599819850139DOI Listing
November 2019

Hippocampal alterations and functional correlates in adolescents and young adults with congenital heart disease.

Hum Brain Mapp 2019 08 9;40(12):3548-3560. Epub 2019 May 9.

Advances in Brain and Child Health Development Research Laboratory, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.

There is a high prevalence of neurodevelopmental impairments in individuals living with congenital heart disease (CHD) and the neural correlates of these impairments are not yet fully understood. Recent studies have shown that hippocampal volume and shape differences may provide unique biomarkers for neurodevelopmental disorders. The hippocampus is vulnerable to early life injury, especially in populations at risk for hypoxemia or hemodynamic instability such as in neonates with CHD. We compared hippocampal gray and white matter volume and morphometry between youth born with CHD (n = 50) aged 16-24 years and healthy peers (n = 48). We also explored whether hippocampal gray and white matter volume and morphometry are associated with executive function and self-regulation deficits. To do so, participants underwent 3T brain magnetic resonance imaging and completed the self-reported Behavior Rating Inventory of Executive Function-Adult version. We found that youth with CHD had smaller hippocampal volumes (all statistics corrected for false discovery rate; q < 0.05) as compared to controls. We also observed significant smaller surface area bilaterally and inward displacement on the left hippocampus predominantly on the ventral side (q < 0.10) in the CHD group that were not present in the controls. Left CA1 and CA2/3 were negatively associated with working memory (p < .05). Here, we report, for the first-time, hippocampal morphometric alterations in youth born with CHD when compared to healthy peers, as well as, structure-function relationships between hippocampal volumes and executive function. These differences may reflect long lasting alterations in brain development specific to individual with CHD.
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http://dx.doi.org/10.1002/hbm.24615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865495PMC
August 2019

Pathogenic variants in AIMP1 cause pontocerebellar hypoplasia.

Neurogenetics 2019 05 28;20(2):103-108. Epub 2019 Mar 28.

Departments of Pediatrics, Neurology & Neurosurgery, MUHC-Research Institute, McGill University, 1001 Blvd Décarie, Montreal, H4A 3J1, Canada.

Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a non-catalytic component of the multi-tRNA synthetase complex which catalyzes the ligation of amino acids to the correct tRNAs. Pathogenic variants in several aminoacyl-tRNA synthetases genes have been linked to various neurological disorders, including leukodystrophies and pontocerebellar hypoplasias (PCH). To date, loss-of-function variants in AIMP1 have been associated with hypomyelinating leukodystrophy-3 (MIM 260600). Here, we report a novel frameshift AIMP1 homozygous variant (c.160delA,p.Lys54Asnfs) in a child with pontocerebellar hypoplasia and simplified gyral pattern, a phenotype not been previously described with AIMP1 variants, thus expanding the phenotypic spectrum. AIMP1 should be included in diagnostic PCH gene panels.
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http://dx.doi.org/10.1007/s10048-019-00572-7DOI Listing
May 2019

Infantile Horner syndrome due to ectopic cervical thymus gland.

Can J Ophthalmol 2019 02 21;54(1):e10-e12. Epub 2018 May 21.

Department of Ophthalmology, McGill University, Montreal, Que.

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http://dx.doi.org/10.1016/j.jcjo.2018.03.019DOI Listing
February 2019

Developmental outcomes in children with congenital cerebellar malformations.

Dev Med Child Neurol 2019 03 15;61(3):350-358. Epub 2018 Oct 15.

Division of Pediatric Neurology, Department of Pediatrics, Neurology/Neurosurgery, Montreal Children's Hospital, McGill University Health Center, Montreal, Canada.

Aim: Neurodevelopmental outcomes in children with congenital cerebellar malformations (CCMs) remain poorly defined. We aimed to assess whether specific neuroimaging features in CCM patients correlate with neurodevelopmental outcomes.

Method: Hospital records and neuroimaging of 67 children with CCMs were systematically reviewed. Logistic regression analyses were used to assess associations between specific imaging features and neurodevelopmental outcomes.

Results: CCM categories were distributed as follows: 28 percent isolated vermis hypoplasia (n=19), 28 percent global cerebellar hypoplasia (n=19), 15 percent Dandy-Walker malformation (n=10), 13 percent pontocerebellar hypoplasia (PCH, n=9), 9 percent molar tooth malformation (n=6), 3 percent rhombencephalosynapsis (n=2), and 3 percent unilateral cerebellar malformation (n=2). Overall, 85 percent (55/65) of the cohort had global developmental delay (GDD). Intellectual disability was present in 61 percent (27/43) and autism spectrum disorder (ASD) in 12 percent (6/52). Adjusting for supratentorial malformations and presence of genetic findings, severe GDD was associated with cerebellar hypoplasia (p=0.049) and PCH (p=0.030), whereas children with vermis hypoplasia were less likely to have severe GDD (p=0.003). Presence of supratentorial abnormalities was not significantly associated with worse neurodevelopmental outcome but was associated with epilepsy.

Interpretation: Children with CCMs have high prevalence of neurodevelopmental deficits. Specific features on imaging can aid prognostication and establish early intervention strategies.

What This Paper Adds: Atypical long-term neurodevelopmental outcome is very common in patients with congenital cerebellar malformations (CCMs). Involvement of the brainstem and cerebellar hemispheres predicts more severe neurodevelopmental disability. Most patients with vermis hypoplasia have language delay but are verbal. Supratentorial abnormalities are not significantly associated with worse neurodevelopmental outcome but are associated with epilepsy. Comorbidities are common in CCMs, especially ophthalmological issues in cerebellar hypoplasia and sensorineural hearing loss in pontocerebellar hypoplasia.
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http://dx.doi.org/10.1111/dmcn.14059DOI Listing
March 2019

Cervical instability in patients with Trisomy 21: The eternal gamble.

Paediatr Anaesth 2018 10 12;28(10):830-833. Epub 2018 Sep 12.

Department of Anesthesia, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada.

Patients with Trisomy 21 are particularly at risk of cervical instability due to ligamentous laxity and osseous abnormalities. Up to 30% of Trisomy 21 patients are affected by atlanto-axial or atlanto-occipital instability, but only 1%-2% of cases are symptomatic. The radiologic assessment of cervical instability is not unanimously considered mandatory. The dynamic cervical spine radiograph is the most common screening tool for ruling out cervical spine instability in patients with Trisomy 21, and it is often requested before surgery. Several measurements have been investigated to assess the presence and degree of cervical instability; however, no conclusive recommendations have been forthcoming. In daily practice, many anesthesiologists may provide anesthesia via such means as laryngoscopy and tracheal intubation during surgery, without any radiological investigations before surgery. This review focuses on the diagnostic and prognostic measures available to evaluate the presence and degree of cervical instability in patients with Trisomy 21 and to propose practical recommendations to be applied in clinical practice.
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http://dx.doi.org/10.1111/pan.13481DOI Listing
October 2018

Trametinib for progressive pediatric low-grade gliomas.

J Neurooncol 2018 Nov 10;140(2):435-444. Epub 2018 Aug 10.

Division of Child Neurology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, 3175 Chemin de la Côte-Sainte-Catherine, Montreal, QC, H3T 1C5, Canada.

Introduction: Pediatric pilocytic astrocytomas (PAs) are low grade gliomas and the most common brain tumors in children. They often represent a therapeutic challenge when incompletely resected as they can recur and progress despite the use of several lines of chemotherapeutic agents or even radiation therapy. Genetic alterations leading to activation of the mitogen-activated-protein-kinase pathway are a hallmark of this disease and offer an interesting therapeutic alternative through the use of targeted inhibitors.

Methods: Here, we describe six children with sporadic PA who were treated with trametinib, a MEK inhibitor, following progression under conventional therapies. Retrospective chart review was performed.

Results: The median age at diagnosis was 2.3 years (y) old [range 11 months (m)-8.5 y old]. KIAA1549-BRAF fusion was identified in five cases, and hotspot FGFR1/NF1/PTPN11 mutations in one. All patients received at least one previous line of chemotherapy (range 1-4). The median time on treatment was 11 m (range 4-20). Overall, we observed two partial responses and three minor responses as best response; three of these patients are still on therapy. Treatment was discontinued in the patient with progressive disease. The most frequent toxicities were minor to moderately severe skin rash and gastro-intestinal symptoms. Two patients had dose reduction due to skin toxicity. Quality of life was excellent with decreased hospital visits and a close to normal life.

Conclusion: Trametinib appears to be a suitable option for refractory pediatric low-grade glioma and warrants further investigations in case of progression.
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http://dx.doi.org/10.1007/s11060-018-2971-9DOI Listing
November 2018

Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel Variant.

Front Neurol 2018 12;9:130. Epub 2018 Mar 12.

Division of Pediatric Neurology, Department of Pediatrics, Montreal Children's Hospital, Montreal, QC, Canada.

Background: Acute hemorrhagic encephalomyelitis (AHEM) is considered as a rare form of acute disseminated encephalomyelitis characterized by fulminant encephalopathy with hemorrhagic necrosis and most often fatal outcome.

Objective: To report the association with Ran Binding Protein ( gene variant and the response to decompressive craniectomy and high-dose intravenous methylprednisolone (IVMP) in life-threatening AHEM.

Design: Single case study.

Case Report: A 6-year-old girl known to have sickle cell disease (SCD) presented an acquired demyelinating syndrome (ADS) with diplopia due to sudden unilateral fourth nerve palsy. She received five pulses of IVMP (30 mg/kg/day). Two weeks after steroid weaning, she developed right hemiplegia and coma. Brain magnetic resonance imaging showed a left frontal necrotico-hemorrhagic lesion and new multifocal areas of demyelination. She underwent decompressive craniotomy and evacuation of an ongoing left frontoparietal hemorrhage. Comprehensive investigations ruled out vascular and infectious process. The neurological deterioration stopped concomitantly with combined neurosurgical drainage of the hematoma, decompressive craniotomy, IVMP, and intravenous immunoglobulins (IVIG). She developed during the following months Crohn disease and sclerosing cholangitis. After 2-year follow-up, there was no new neurological manifestation. The patient still suffered right hemiplegia and aphasia, but was able to walk. Cognitive/behavioral abilities significantly recovered. A heterozygous novel rare missense variant (c.4993A>G, p.Lys1665Glu) was identified in 2, a gene associated with acute necrotizing encephalopathy. RANBP2 is a protein playing an important role in the energy homeostasis of neuronal cells.

Conclusion: In any ADS occurring in the context of SCD and/or autoimmune condition, we recommend to slowly wean steroids and to closely monitor the patient after weaning to quickly treat any recurrence of neurological symptom with IVMP. This case report, in addition to others, stresses the likely efficacy of combined craniotomy, IVIG, and IVMP treatments in AHEM. mutations may sensitize the brain to inflammation and predispose to AHEM.
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http://dx.doi.org/10.3389/fneur.2018.00130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857578PMC
March 2018

Intrathyroidal thymic tissue in children: Avoiding unnecessary surgery.

J Pediatr Surg 2018 May 8;53(5):1010-1013. Epub 2018 Feb 8.

Division of Pediatric General and Thoracic Surgery, The Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada. Electronic address:

Background/purpose: Intrathyroidal thymic tissue may be misinterpreted as a thyroid lesion in children, leading to invasive tests or resection. We sought to describe the characteristic imaging features of these lesions and to evaluate the safety of non-operative management.

Methods: A retrospective review of all patients less than 18years old with intrathyroidal thymic tissue from 2000 to 2016 was performed. Data collection included patient demographics, imaging results, interventions, and outcomes.

Results: Eleven patients were identified using institutional radiology and pathology databases. Median patient age and lesion size at presentation were 5years old (range 2 to 8years old) and 0.9cm (range 0.4 to 9.2cm), respectively. Six lesions were incidentally identified, six were left-sided, and the most common location was the lower pole. Ultrasonographic features were reproducible and included well demarcated (10/11), hypoechoic lesions (11/11), containing punctate/linear internal echoes (11/11), and occasional mild hypervascularity (6/11). All cases demonstrated interval size and echotexture stability over a median surveillance period of 3years (range 1 to 8years). While 9 patients were simply observed, the first patient in this series underwent excision, while another had a fine needle aspiration to confirm pathology.

Level Of Evidence: Study of diagnostic test, Level IV.

Conclusion: Intrathyroidal thymic tissue has typical clinical and sonographic characteristics which allow for appropriate diagnosis and avoids thyroid resection.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.02.011DOI Listing
May 2018

Illness Severity Predicts Death and Brain Injury in Asphyxiated Newborns Treated with Hypothermia.

Am J Perinatol 2018 08 16;35(10):951-958. Epub 2018 Feb 16.

Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Canada.

Objective: To determine if illness severity during the first days of life predicts adverse outcome in asphyxiated newborns treated with hypothermia.

Study Design: We conducted a retrospective cohort study of asphyxiated newborns treated with hypothermia. Illness severity was calculated daily during the first 4 days of life using the Score for Neonatal Acute Physiology II (SNAP-II score). Adverse outcome (death and/or brain injury) was recorded. Differences in SNAP-II scores between the newborns with and without adverse outcome were assessed.

Result: 214 newborns were treated with hypothermia. The average SNAP-II score over the first 4 days of life was significantly worse in newborns developing adverse outcome. The average SNAP-II score was an excellent predictor of death (area under the curve [AUC]: 0.93; < 0.001) and a fair predictor of adverse outcome (AUC: 0.73; < 0.001). The average SNAP-II score remained a significant predictor of adverse outcome (odds ratio [95% confidence interval]: 1.08 [1.04-1.12]; < 0.001), after adjusting for baseline characteristics, degree of initial asphyxial event, and initial severity of encephalopathy.

Conclusion: In asphyxiated newborns treated with hypothermia, not only the initial asphyxial event but also the illness severity during the first days of life was a significant predictor of death or brain injury.
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http://dx.doi.org/10.1055/s-0038-1632368DOI Listing
August 2018

Prediction of outcome in asphyxiated newborns treated with hypothermia: Is a MRI scoring system described before the cooling era still useful?

Eur J Paediatr Neurol 2018 May 31;22(3):387-395. Epub 2018 Jan 31.

Division of Newborn Medicine, Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Canada. Electronic address:

Aim: To determine whether an MRI scoring system, which was validated in the pre-cooling era, can still predict the neurodevelopmental outcome of asphyxiated newborns treated with hypothermia at 2 years of age.

Patients And Method: We conducted a retrospective cohort study of asphyxiated newborns treated with hypothermia. An MRI scoring system, which was validated in the pre-cooling era, was used to grade the severity of brain injury on the neonatal brain MRI. Their neurodevelopment was assessed around 2 years of age; adverse outcome included cerebral palsy, global developmental delay, and/or epilepsy.

Results: One hundred and sixty-nine newborns were included. Among the 131 newborns who survived and had a brain MRI during the neonatal period, 92% were evaluated around 2 years of age or later. Of these newborns, 37% displayed brain injury, and 23% developed an adverse outcome. Asphyxiated newborns treated with hypothermia who had an adverse outcome had a significantly higher MRI score (p <0.001) compared to those without an adverse outcome.

Conclusion: An MRI scoring system that was validated before the cooling era is still able to reliably differentiate which of the asphyxiated newborns treated with hypothermia were more prone to develop an adverse outcome around 2 years of age.
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http://dx.doi.org/10.1016/j.ejpn.2018.01.017DOI Listing
May 2018

Hypotension and Brain Injury in Asphyxiated Newborns Treated with Hypothermia.

Am J Perinatol 2018 01 31;35(1):31-38. Epub 2017 Jul 31.

Department of Pediatrics, McGill University, Montreal Children's Hospital, Montreal, Canada.

Objective: This study aimed to assess the incidence of hypotension in asphyxiated newborns treated with hypothermia, the variability in treatments for hypotension, and the impact of hypotension on the pattern of brain injury.

Study Design: We conducted a retrospective cohort study of asphyxiated newborns treated with hypothermia. Mean blood pressures, lactate levels, and inotropic support medications were recorded during the hospitalization. Presence and severity of brain injury were scored using the brain magnetic resonance imaging (MRI) obtained after the hypothermia treatment was completed.

Results: One hundred and ninety term asphyxiated newborns were treated with hypothermia. Eighty-one percent developed hypotension. Fifty-five percent of the newborns in the hypotensive group developed brain injury compared with 35% of the newborns in the normotensive group ( = 004). Twenty-nine percent of the newborns in the hypotensive group developed severe brain injury, compared with only 15% in the normotensive group. Nineteen percent of the newborns presenting with volume- and/or catecholamine-resistant hypotension had near-total injury, compared with 6% in the normotensive group and 8% in the group responding to volume and/or catecholamines.

Conclusion: Hypotension was common in asphyxiated newborns treated with hypothermia and was associated with an increased risk of (severe) brain injury in these newborns.
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http://dx.doi.org/10.1055/s-0037-1604392DOI Listing
January 2018

Early Imaging and Adverse Neurodevelopmental Outcome in Asphyxiated Newborns Treated With Hypothermia.

Pediatr Neurol 2017 Aug 19;73:20-27. Epub 2017 May 19.

Division of Newborn Medicine, Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Canada. Electronic address:

Background: Brain injury can be identified as early as day two of life in asphyxiated newborns treated with hypothermia, when using diffusion magnetic resonance imaging (MRI). However, it remains unclear whether these diffusion changes can predict future neurodevelopment. This study aimed to determine whether abnormal early diffusion changes in newborns treated with hypothermia are associated with adverse neurodevelopmental outcome at age two years.

Methods: Asphyxiated newborns treated with hypothermia were enrolled prospectively. They underwent magnetic resonance imaging (MRI) at specific time points over the first month of life, including diffusion-weighted imaging and diffusion-tensor imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in different regions of interest. Adverse neurodevelopmental outcome was defined as cerebral palsy, global developmental delay, and/or seizure disorder around age two years. ADC and FA values were compared between the newborns developing or not developing adverse outcome.

Results: Twenty-nine asphyxiated newborns treated with hypothermia were included. Among the newborns developing adverse outcome, ADC values were significantly decreased on days two to three of life and increased around day ten of life in the thalamus, posterior limb of the internal capsule, and the lentiform nucleus. FA values decreased in the same regions around day 30 of life. These newborns also had increased ADC around day ten of life and around day 30 of life, and decreased FA around day 30 of life in the anterior and posterior white matter.

Conclusions: Diffusion changes that were evident as early as day two of life, when the asphyxiated newborns were still treated with hypothermia, were associated with later abnormal neurodevelopmental outcome.
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http://dx.doi.org/10.1016/j.pediatrneurol.2017.04.025DOI Listing
August 2017

Clinical and Radiologic Spectrum of Septo-optic Dysplasia: Review of 17 Cases.

J Child Neurol 2017 08 8;32(9):797-803. Epub 2017 May 8.

2 Departments of Pediatrics, Neurology, and Neurosurgery, McGill University, Montreal, Quebec, Canada.

We retrospectively reviewed the clinical and radiologic characteristics of 17 individuals with septo-optic dysplasia (SOD) and attempted to identify correlations between imaging findings, clinical features, and neurodevelopmental outcome. Surprisingly, only 1 (6%) individual was classified as classic SOD (with septum pellucidum/corpus callosum dysgenesis), 3 (18%) as SOD-like (with normal septum pellucidum/corpus callosum) and the majority, 13 (76%), as SOD-plus (with cortical brain malformation). Cortical abnormalities included schizencephaly, polymicrogyria, and gray matter heterotopias. All individuals had optic nerve hypoplasia, 11 (65%) had endocrinologic deficits, and 13 (76%) had abnormal cerebral midlines. Seven individuals (41%) had all 3 features. Neurodevelopmental outcome was abnormal in 13 (78%), ranging from mild to severe developmental delay. Individuals with SOD-plus did not have more severe neurologic deficits than individuals with classic or SOD-like subgroups. Thus, SOD is clinically and radiologically heterogeneous, and cortical abnormalities are very common. Neurodevelopmental deficits are very prevalent, and of wide-ranging severity.
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http://dx.doi.org/10.1177/0883073817707300DOI Listing
August 2017