Martin Bunge

Neuroimaging findings in pediatric sports-related concussion.

OBJECT The goal in this review was to summarize the results of clinical neuroimaging studies performed in patients with sports-related concussion (SRC) who were referred to a multidisciplinar ypediatric concussion program. METHODS The authors conducted a retrospective review of medical records and neuroimaging findings for all patients referred to a multidisciplinary pediatric concussion program between September 2013 and July 2014. Inclusion criteria were as follows: 1) age ≤ 19 years; and 2) physician-diagnosed SRC. All patients underwent evaluation and follow-up by the same neurosurgeon. The 2 outcomes examined in this review were the frequency of neuroimaging studies performed in this population (including CT and MRI) and the findings of those studies. Clinical indications for neuroimaging and the impact of neuroimaging findings on clinical decision making were summarized where available. This investigation was approved by the local institutional ethics review board. RESULTS A total of 151 patients (mean age 14 years, 59% female) were included this study. Overall, 36 patients (24%) underwent neuroimaging studies, the results of which were normal in 78% of cases. Sixteen percent of patients underwent CT imaging; results were normal in 79% of cases. Abnormal CT findings included the following: arachnoid cyst (1 patient), skull fracture (2 patients), suspected intracranial hemorrhage (1 patient), and suspected hemorrhage into an arachnoid cyst (1 patient). Eleven percent of patients underwent MRI; results were normal in 75% of cases. Abnormal MRI findings included the following: intraparenchymal hemorrhage and sylvian fissure arachnoid cyst (1 patient); nonhemorrhagic contusion (1 patient); demyelinating disease (1 patient); and posterior fossa arachnoid cyst, cerebellar volume loss, and nonspecific white matter changes (1 patient). CONCLUSIONS Results of clinical neuroimaging studies are normal in the majority of pediatric patients with SRC. However, in selected cases neuroimaging can provide information that impacts decision making about return to play and retirement from the sport.

Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome

OBJECT A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow (CBF) and cerebrovascular responsiveness in individual patients with concussion remains elusive. Here the authors summarize the safety, feasibility, and results of brain CO2 stress testing in adolescents with postconcussion syndrome (PCS) and healthy controls. METHODS This study was approved by the Biomedical Research Ethics Board at the University of Manitoba. Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI, pseudo-continuous arterial spin labeling MRI, and brain stress testing using controlled CO2 challenge and blood oxygen level-dependent (BOLD) MRI. Post hoc processing was performed using statistical parametric mapping to determine voxel-by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO2 stimulus (increase in BOLD signal) or the inverse (decrease in BOLD signal). Receiver operating characteristic (ROC) curves were generated to compare voxel counts categorized by control (0) or PCS (1). RESULTS Studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study participants. No differences in CO2 stimuli were seen between the 2 participant groups. No group differences in global mean CBF were detected between PCS patients and healthy controls. Patient-specific differences in mean regional CBF and CO2 BOLD responsiveness were observed in all PCS patients. The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas (that is, abnormal voxel counts) produced an area under the curve of 0.87 (p < 0.0001) and 0.80 (p = 0.0003), respectively, consistent with a clinically useful predictive model. CONCLUSIONS Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF. Future prospective studies are warranted to examine the utility of brain MRI CO2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS.

A V139M mutation also causes the reversible CNS phenotype in CMTX.

X-linked Charcot Marie Tooth disease (CMTX; OMIM # 320800) is the second most common cause of inherited demyelinating neuropathy and is caused by mutations in the GJB1 ( also referred to as connexin 32) gene coding for the gap junction protein connexin 32 (Cx32). Cx32 is expressed in the myelinating Schwann cells in the peripheral nervous system (PNS) and in oligodendrocytes in the central nervous system (CNS). Gap junctions help rapid transport of ions and small molecules across cell membranes.1 Various central nervous system manifestations (clinical and subclinical) in CMTX have been reported.2-9 In the last ten years a distinct, reversible clinical syndrome associated with pyramidal and or bulbar weakness and concomitant transient magnetic resonance imaging (MRI) findings of diffuse, confluent white matter abnormalities has been increasingly reported.10-13 All 11 patients reported in the published English literature since 1998, when the above syndrome was first described, have various mutations in the GJB1 gene causing dysfunctional gap junctions. We report two brothers who presented with pyramidal weakness, dysarthria, ataxia and bulbar weakness a year apart predating their genomic CMTX diagnosis. Both boys and their mother were later confirmed to have a V139M mutation in the GJB1 gene. Computed tomography (CT), magnetic resonance imaging and magnetic resonance spectroscopy (MRS) features of one of the brothers are described.

Diffuse hemangiomatosis with predominant central nervous system involvement.

Diffuse neonatal hemangiomatosis presents with multiple, progressive, rapidly growing cutaneous hemangiomas associated with widespread visceral hemangiomas in the liver, lungs, gastrointestinal tract, brain, and meninges. Described here is a case of diffuse neonatal hemangiomatosis with predominant central nervous system involvement. The early appearance of central nervous system lesions on imaging can overlap with that of cavernous malformations, confounding diagnosis; however, rapid growth, response to steroids, cystic appearance with sedimentation levels of the mature lesions, and involvement of other visceral organs can help confirm the diagnosis.

Multidisciplinary management of pediatric sports-related concussion

OBJECTIVES To summarize the clinical characteristics and outcomes of pediatric sports-related concussion (SRC) patients who were evaluated and managed at a multidisciplinary pediatric concussion program and examine the healthcare resources and personnel required to meet the needs of this patient population. METHODS We conducted a retrospective review of all pediatric SRC patients referred to the Pan Am Concussion Program from September 1st, 2013 to May 25th, 2015. Initial assessments and diagnoses were carried out by a single neurosurgeon. Return-to-Play decision-making was carried out by the multidisciplinary team. RESULTS 604 patients, including 423 pediatric SRC patients were evaluated at the Pan Am Concussion Program during the study period. The mean age of study patients was 14.30 years (SD: 2.32, range 7-19 years); 252 (59.57%) were males. Hockey (182; 43.03%) and soccer (60; 14.18%) were the most commonly played sports at the time of injury. Overall, 294 (69.50%) of SRC patients met the clinical criteria for concussion recovery, while 75 (17.73%) were lost to follow-up, and 53 (12.53%) remained in active treatment at the end of the study period. The median duration of symptoms among the 261 acute SRC patients with complete follow-up was 23 days (IQR: 15, 36). Overall, 25.30% of pediatric SRC patients underwent at least one diagnostic imaging test and 32.62% received referral to another member of our multidisciplinary clinical team. CONCLUSION Comprehensive care of pediatric SRC patients requires access to appropriate diagnostic resources and the multidisciplinary collaboration of experts with national and provincially-recognized training in TBI.

Prolonged Survival and Serial Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy Changes in Infantile Krabbe Disease

Krabbe disease may present during infancy, late infancy, or adulthood. Earlier-onset disease is associated with shorter survival times. We present a case of infantile onset Krabbe disease with prolonged survival, initial intracranial optic nerves and optic chiasm hypertrophy, and serial changes on cranial magnetic resonance imaging and magnetic resonance spectroscopy.

Another case of Varadi–Papp Syndrome with a molar tooth sign

We read with interest the article by Gleeson et al. [2004] entitled. ‘‘Molar Tooth Sign of the Midbrain–Hindbrain Junction: Occurrence in Multiple Distinct Syndromes.’’ The molar tooth sign was previously considered pathognomonic of Joubert Syndrome. The authors illustrate that this finding can be present in other syndromes as well. In the article they describe two cases with Varadi–Papp Syndrome or Orofaciodigital Syndrome type VI, where the molar tooth sign was seen. The authors state that they believe the molar tooth sign is a frequent component of this syndrome based on these two cases, and given that posterior fossa abnormalities have been previously reported in patients. Unfortunately, the authors were not able to evaluate other patients with Varadi–Papp Syndrome to determine if they also had a molar tooth sign. We would therefore like to describe our experience with a child with Varadi–Papp Syndrome. The patient was born to a G13, P10, and SA2 woman at 39-week gestation. The mother had little prenatal care but denied exposures to teratogens. One sister has a Tetralogy of Fallot secondary to a 22q11.2 deletion. A half-sister has aortic, mitral, and pulmonary valve stenosis. The parents are both of Aboriginal Canadian origin. There is no known consanguinity. The diagnosis of Varadi–Papp syndrome made was based on the presence of multiple anomalies including preand post-axial polysyndactyly, a midline cleft lip, cleft palate, small tongue, and multiple alveolar frenula. Both hands had eight digits (Fig. 1) and both feet had seven digits (Fig. 2). A Y-shaped metacarpal was noted on the left hand. Other problems included visual impairment, developmental delay, hypotonia, airway obstruction requiring tracheostomy, cryptorchidism, and a bicuspid aortic valve. He had a normal karyotype, that is, 46,XY. FISH studies showed that he did not have the 22q11.2 deletion, seen in his sister. MRI imaging was done. The superior vermis was dysplastic, with a sagital midline cleft. The superior cerebellar peduncles was thickened and mal-orientated. The anterior-posterior dimension of the pons was reduced, resulting in a deep interpeduncular cleft. These latter findings resulted in a molar tooth configuration of the upper pons (Fig. 3). The superior aspect of the fourth ventricle had a ‘‘batwing’’ configuration. This case therefore supports the conclusion of Gleeson et al. [2004] that the molar tooth sign is a frequent component of Varadi–Papp syndrome and that this syndrome should be considered as one of the Joubert Syndrome Related Disorders.

A computer-aided change detection system for paediatric acute intracranial haemorrhage

In this paper, we apply computer science and software engineering techniques in, and bring benefits to, real-life applications. Specifically, we propose a design for a computeraided change detection system, which uses both image processing and data mining techniques, to help clinicians diagnose bleeding in childrens brains---i.e., in medical terms, paediatric acute intracranial haemorrhage (AIH). The proposed system provides clinicians with computerized analysis of medical images in the form of computed tomography (CT) scans of the heads of children patients. This, in turn, leads to more efficient detection, diagnosis, and progress evaluation of paediatric AIH.

Increasing incidence of optic nerve hypoplasia/septo-optic dysplasia spectrum: Geographic clustering in Northern Canada

Introduction Owing to the shared embryonic origin, defects in development of optic nerves are often seen in conjunction with defects affecting the surrounding brain and pituitary gland. Optic nerve hypoplasia (ONH) and septo-optic dysplasia (SOD) represent a clinical spectrum associated with visual, pituitary and severe central nervous system structural abnormalities (SODplus). Based on changing clinical patterns, our primary objective was to examine trends in annual incidence of ONH/SOD and geographical clustering in Manitoba. Methods This was a retrospective 1996 to 2015 chart review with extraction of anthropometric measures, radiologic findings, parental characteristics, endocrinopathies and neurologic symptoms from all involved in care. Postal codes were used to assign map co-ordinates and identify relevant census-based deprivation indices. Results Ninety-three children were identified in our catchment area; Poisson regression confirmed a striking 1.11-fold annual increase (95% confidence interval 1.07 to 1.16) or ~800% over two decades. The annual incidence (averaged 2010 to 2014 chart data) reached 53.3 per 100,000, affecting 1 in 1875 live births. Most (~55%) had SODplus. Common presenting features were hypoglycemia, nystagmus, seizures and developmental delay; 40% had hormone deficiencies; 80% had reduced visual acuity, typically bilateral. Many were premature with young, primiparous mothers. Unhealthy maternal lifestyles and severe material deprivation were noted. There was disproportionate clustering in individuals from Northern Manitoba at three times the average provincial rate. Conclusion We noted a dramatic rise in the annual incidence of ONH/SOD, which was strongly associated with poverty and northern communities. The pattern was consistent with environmental or nutritional etiologies. Many children were severely affected with increased morbidity and health care burdens.

Evolving Pediatric Cerebral Arteriopathy on Neuroimaging

Background: Progressive cerebral arteriopathies are not an uncommon cause of ischemic stroke in children. The clinical and radiological distinction between various cerebral arteriopathies remains a challenge and topic of controversy for physicians. Methods: We report an 11-year-old girl who presented with a left subcortical ischemic stroke. Results: An 11-year-old girl presented with a progressive right hemiparesis. Her neuroimaging showed diffusion restriction and T2 signal abnormalities in the left basal ganglia with normal magnetic resonance and CT angiography. Subsequent MRA and cerebral catheter angiography at 9 days post-stroke revealed medium and large vessel stenoses of bilateral distal anterior cerebral arteries, proximal and distal segment of left middle cerebral artery, and distal left internal cerebral artery. Conclusion: This case demonstrates the uncertainties and challenges related to ischemic stroke due to cerebral arteriopathies and the importance of early evaluation with cerebral catheter angiogram with unidentified ischemic stroke etiology and normal initial non-invasive angiography.