Publications by authors named "Maryam Oskoui"

81 Publications

Therapeutic interventions for spinal muscular atrophy: preclinical and early clinical development opportunities.

Expert Opin Investig Drugs 2021 Apr 13:1-9. Epub 2021 Apr 13.

Departments of Pediatrics and Neurology & Neurosurgery, McGill University, Montreal, QC, Canada.

Introduction: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative neuromuscular disease that presents primarily in children. Abnormalities in the gene cause reduced levels of the survival motor neuron (SMN) protein, while a second gene, , produces low levels of functional SMN protein. Currently available drugs do not cure, so a significant unmet need remains for patients treated after symptom onset.

Areas Covered: Drugs available in the clinic, investigational agents and key questions for researchers are discussed. A pragmatic search of the literature was performed to identify therapies in late stages of preclinical, or in early stages of clinical development. This list was compared to the CureSMA pipeline for completeness. Drugs approved for indications that have potential for impact for SMA were included. These drugs target the primary deficiency in SMN protein or other pathways involved in SMA pathophysiology that are not SMN-protein dependent.

Expert Opinion: Children treated after the onset of symptoms continue to have significant disability. Given the heterogeneity of the population phenotype evidenced by variable response to initial therapy, age at treatment onset and the need to demonstrate added value beyond approved therapeutics, the clinical development of new drugs will be challenging.
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http://dx.doi.org/10.1080/13543784.2021.1904889DOI Listing
April 2021

Validation of home portable monitoring for the diagnosis of sleep-disordered breathing in adolescents and adults with neuromuscular disorders.

J Clin Sleep Med 2021 Mar 19. Epub 2021 Mar 19.

Respiratory & Epidemiology and Clinical Research Unit, Translational Research in Respiratory Diseases Program, McGill University Health Centre, Montreal, Quebec, Canada.

Study Objectives: Sleep-disordered breathing (SDB) is common in patients with neuromuscular disorders (NMD), developing before chronic hypercapnia appears. Polysomnography (PSG) is the diagnostic gold standard but is often impractical and poorly accessible for individuals with NMD. We sought to determine diagnostic accuracy, feasibility and patient preference of Home Sleep Apnea Testing (HSAT) compared with PSG for detection of SDB in NMD.

Methods: Participants with NMD at risk for SDB, aged ≥13 years, underwent HSAT followed by overnight PSG with concomitant Laboratory Sleep Apnea Testing (same device as HSAT). Sensitivity and specificity were calculated for standard Apnea-Hypopnea Index (AHI) cut-offs for mild (≥5/h), moderate (≥15/h) and severe SDB (≥30/h), and for Oxygen Desaturation Index (ODI) ≥5/h. Receiver operating characteristic (ROC) curves were built. A questionnaire assessed patient preference.

Results: Of 38 participants, 73% had moderate-severe SDB and 79% had technically acceptable HSAT. For AHI ≥15/h, HSAT sensitivity and specificity were 50% and 88% respectively. For ODI ≥5/h, HSAT sensitivity and specificity were 95% and 78%, respectively. The area under the ROC curve for AHI ≥15 was 0.88 (95% CI 0.69-1.00) for HSAT. The HSAT underestimated the AHI from PSG (bias -10.7 ±15.9). HSAT was preferred to PSG by 61% of participants.

Conclusions: HSAT is feasible, preferred by patients, and reliable for detecting SDB in most cases although it cannot definitively rule out SDB. Therefore, HSAT is a viable diagnostic approach for SDB in NMD when PSG is not feasible, recognizing that it does not accurately distinguish between upper airway obstruction and hypoventilation. Additional work is needed to further optimize home sleep testing in NMD.
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http://dx.doi.org/10.5664/jcsm.9254DOI Listing
March 2021

Improving Care and Empowering Adults Living with SMA: A Call to Action in the New Treatment Era.

J Neuromuscul Dis 2021 Feb 24. Epub 2021 Feb 24.

MDUK Neuromuscular Center, Department of Paediatrics, University of Oxford, Oxford, UK.

While Spinal Muscular Atrophy (SMA) has historically been managed with supportive measures, the emergence of innovative medicines has given those living with SMA hope for improved quality of life and has revolutionized care. Despite these advances, the use of therapies and changes in disease management strategies have focused on pediatric populations, leaving adults living with SMA, and those transitioning into adulthood, relatively neglected. Through a multi-faceted approach that gathered unbiased perspectives from clinical experts, validated insights from individuals with lived experiences, and substantiated findings with evidence from the literature, we have exposed unmet needs that are hindering the field and, ultimately, impacting care and quality of life for adults living with SMA. Here, we set new aspirations and calls to action to inspire continued research in this field, stimulate dialogue across the SMA community and inform policies that deliver effective management and care throughout an adult's journey living with SMA.
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http://dx.doi.org/10.3233/JND-200611DOI Listing
February 2021

Reldesemtiv in Patients with Spinal Muscular Atrophy: a Phase 2 Hypothesis-Generating Study.

Neurotherapeutics 2021 Feb 23. Epub 2021 Feb 23.

Stanford University, Stanford, CA, USA.

This phase 2, double-blind, placebo-controlled, hypothesis-generating study evaluated the effects of oral reldesemtiv, a fast skeletal muscle troponin activator, in patients with spinal muscular atrophy (SMA). Patients ≥ 12 years of age with type II, III, or IV SMA were randomized into 2 sequential, ascending reldesemtiv dosing cohorts (cohort 1: 150 mg bid or placebo [2:1]; cohort 2: 450 mg bid or placebo [2:1]). The primary objective was to determine potential pharmacodynamic effects of reldesemtiv on 8 outcome measures in SMA, including 6-minute walk distance (6MWD) and maximum expiratory pressure (MEP). Changes from baseline to weeks 4 and 8 were determined. Pharmacokinetics and safety were also evaluated. Patients were randomized to reldesemtiv 150 mg, 450 mg, or placebo (24, 20, and 26, respectively). The change from baseline in 6MWD was greater for reldesemtiv 450 mg than for placebo at weeks 4 and 8 (least squares [LS] mean difference, 35.6 m [p = 0.0037] and 24.9 m [p = 0.058], respectively). Changes from baseline in MEP at week 8 on reldesemtiv 150 and 450 mg were significantly greater than those on placebo (LS mean differences, 11.7 [p = 0.038] and 13.2 cm HO [p = 0.03], respectively). For 6MWD and MEP, significant changes from placebo were seen in the highest reldesemtiv peak plasma concentration quartile (C > 3.29 μg/mL; LS mean differences, 43.3 m [p = 0.010] and 28.8 cm HO [p = 0.0002], respectively). Both dose levels of reldesemtiv were well tolerated. Results suggest reldesemtiv may offer clinical benefit and support evaluation in larger SMA patient populations.
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http://dx.doi.org/10.1007/s13311-020-01004-3DOI Listing
February 2021

Transient hyperreflexia: An early diagnostic clue in later-onset spinal muscular atrophy.

Neurol Clin Pract 2020 Dec;10(6):e66-e67

Departments of Pediatric and Neurology/Neurosurgery (MO) and Faculty of Medicine (DHK), McGill University, Montréal, QC, Canada; and Departments of Pathology and Cell Biology and Neurology (GZM), Center for Motor Neuron Biology and Disease (GZM, DCDV), and Departments of Neurology and Pediatrics (DCDV), Columbia University, New York.

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http://dx.doi.org/10.1212/CPJ.0000000000000810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837431PMC
December 2020

Look Around Me: Environmental and Socio-Economic Factors Related to Community Participation for Children with Cerebral Palsy in Québec.

Phys Occup Ther Pediatr 2021 Jan 25:1-18. Epub 2021 Jan 25.

School of Physical and Occupational Therapy, McGill University, Montreal, Canada.

This study aimed at gaining a deeper understanding of the environmental and socio-economic factors affecting participation outcomes in community and leisure activities for children with disabilities, as well as the trajectories of participation for these children to promote their health and guarantee their rights are respected. A participatory action research (PAR) approach and linear regression analysis were employed to identify contextual factors associated with the community participation of children with cerebral palsy (CP) living in Quebec, Canada. Stakeholders engaged through the entire research process supported the development of questionnaires, data collection, analysis and interpretation of results. Neighborhood outings were ranked among the most practiced activities by children with CP. Only in a few cases (9%) did children participate in more than two types of activities outside of school. Factors limiting children's participation were predominantly extrinsic in origin, including financial burden and lack of information about existing opportunities. There is a serious need for communities and local governments to inform parents about available resources, programs and policies that can support their child's participation. Rehabilitation professionals could partner with stakeholders to inform the development of public policies that target the identified barriers and promote children's integration and fulfillment.
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http://dx.doi.org/10.1080/01942638.2020.1867693DOI Listing
January 2021

Cerebral palsy in Canadian Indigenous children.

Dev Med Child Neurol 2021 May 13;63(5):614-622. Epub 2020 Dec 13.

Department of Pediatrics, McGill University, Montreal, Quebec, Canada.

Aim: To determine whether inequities in health outcomes for Indigenous Canadians are also present in cerebral palsy (CP) by comparing CP profiles between Indigenous and non-Indigenous children.

Method: Using the Canadian Cerebral Palsy Registry, we conducted a cross-sectional study. CP motor subtype, gross motor severity, comorbidities, perinatal adversity, preterm birth, and parental education were compared between 94 Indigenous (53 males, 41 females) and 1555 non-Indigenous (891 males, 664 females) children (all >5y). Multivariate analysis was done to analyze adverse CP factors, defined as CP gross motor severity and comorbidities. CP etiologies, either prenatal/perinatal or postnatal, were also compared.

Results: Indigenous children with CP have higher odds of having low parental education (odds ratio [OR] 6.15, 95% confidence interval [CI] 3.36-11.3) and comorbidities (OR 4.46, 95% CI 1.62-12.3), especially cognitive (OR 4.52, 95% CI 2.27-9.05), communication (OR 2.66, 95% CI 1.54-4.61), and feeding (OR 2.25, 95% CI 1.33-3.83) impairment. Indigenous children also have higher CP gross motor severity (p=0.03). Indigenous children are also more likely to have non-accidental head injury (n=4; OR 8.18, 95% CI 1.86-36.0) as the cause of their postnatal CP.

Interpretation: Indigenous populations have worse health outcomes as a result of intergenerational impacts of colonization. Our study shows that Indigenous children with CP have increased comorbidities and higher CP gross motor severity, reinforcing the need for a multidisciplinary approach to management. Furthermore, targeted prevention programs against preventable causes of CP, such as non-accidental head injury, may be beneficial.

What This Paper Adds: Indigenous children with cerebral palsy (CP) have more severe motor impairment and more comorbidities. Non-accidental head injury is a significant cause of postnatal CP.
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http://dx.doi.org/10.1111/dmcn.14776DOI Listing
May 2021

Emergency Department Use in Children with Cerebral Palsy: A Data Linkage Study.

Can J Neurol Sci 2020 Oct 7:1-6. Epub 2020 Oct 7.

Departments of Pediatrics and Neurology & Neurosurgery, McGill University, Montréal, Quebec, Canada.

Objective: To describe the pattern of emergency department (ED) consultations in children with cerebral palsy (CP) compared to controls and factors predictive of ED consultations.

Methods: This retrospective cohort study linked data from the Registre de la paralysie cérébrale du Québec (REPACQ) and provincial administrative health databases. The CP cohort was comprised of children enrolled in REPACQ born between 1999 and 2002. REPACQ covers 6 of 17 Quebec health administrative regions. Region-, age-, and gender-matched controls were identified from administrative health databases in a 20:1 ratio. The primary outcome was high use of ED services (≥4 ED visits during the study period). Relative risk (RR) and 95% confidence interval (CI) were calculated.

Results: In total, 301 children with CP were linked to administrative data and 6040 peer controls were selected. Ninety-two percent (92%) of the CP cohort had at least one ED visit in the study period, compared to 74% among controls (RR 1.24, 95% CI 1.19-1.28). Children with CP were more likely than their peers to have high ED use (RR 1.40; 95% CI 1.30-1.52). Factors predictive of high ED use were comorbid epilepsy (RR 1.23; 95% CI 1.04-1.46) and severity of motor impairment (RR 1.14; 95% CI 0.95-1.37).

Conclusion: Children with CP are more likely to present to the ED than their peers, resulting in increased use of ED services. Coordinated care with improved access to same-day evaluations could decrease ED use. Health system factors and barriers should be investigated to ensure optimal and appropriate use of ED services.
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http://dx.doi.org/10.1017/cjn.2020.217DOI Listing
October 2020

Hospitalizations in School-Aged Children with Cerebral Palsy and Population-Based Controls.

Can J Neurol Sci 2020 Sep 11:1-8. Epub 2020 Sep 11.

Departments of Pediatrics and Neurology & Neurosurgery, McGill University, Montréal, QC, Canada.

Objective: To compare hospitalizations among children with cerebral palsy (CP) and healthy controls and to identify factors associated with hospitalizations in children with CP.

Methods: This retrospective cohort study linked data from a provincial CP Registry and administrative health databases. The CP cohort was comprised of children born from 1999 to 2002. Age, sex, and region-matched controls were identified from administrative health databases. Mean differences, relative risk (RR), and 95% confidence intervals (CIs) were calculated.

Results: A total of 301 children with CP were linked to administrative health data and matched to 6040 controls. Mean hospitalizations per child during the study period were higher in children with CP compared to controls (raw mean difference (RMD) 5.0 95% CI 4.7 to 5.2) with longer length of stay (RMD 2.8 95% CI 1.8 to 3.8) and number of diagnoses per hospitalization (RMD 1.6 95% CI 1.4 to 1.8). Increased risk of hospitalization was observed in non-ambulant children with CP (RR 1.12 95% CI 1.01 to 1.22) compared to ambulant children and among those with spastic tri/quadriplegic CP compared to other CP subtypes (RR 1.15, 95% CI 1.05 to 1.27). Feeding difficulties (RR 1.20 95% CI 1.13 to 1.27), cortical visual (RR 1.22 95% CI 1.13 to 1.32), cognitive (RR 1.16 95% CI 1.04 to 1.30), and communication impairment (RR 1.26 95% CI 1.10 to 1.44) were associated with increased hospitalizations.

Conclusions: Children with CP face more frequent, longer hospital stays than peers, especially those with a more severe CP profile. Coordinated interdisciplinary care is needed in school-aged children with CP and medical complexity.
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http://dx.doi.org/10.1017/cjn.2020.199DOI Listing
September 2020

Complementary and Alternative Therapy Use in Children with Cerebral Palsy.

Can J Neurol Sci 2020 Aug 28:1-7. Epub 2020 Aug 28.

Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

Objective: To describe complementary and alternative medicine (CAM) use amongst children with cerebral palsy (CP) in Canada and to identify factors associated with CAM use.

Methods: We conducted a cross-sectional study, utilising data from the Canadian CP Registry. We explored the association between CAM use and regional, socioeconomic and CP phenotypic variables, and parental perception of the family-centredness of clinical care using the Measures of Process of Care-56 (MPOC-56). Chi-square analyses were performed, and odds ratios (OR) and 95% confidence intervals (CI) were obtained. Mann-Whitney U tests were used to compare MPOC-56 scores between CAM users and non-CAM users.

Results: The study sample consisted of 313 families of which 27% reported CAM use in the past year. Children with CP using CAM were more likely to reside in Western Canada (OR 3.3, 95% CI 1.6-6.7), live in a two-parent household (OR 3.5, 95% CI 1.5-8.4), have an ataxic/hypotonic or dyskinetic CP subtype (OR 3.0, 95% CI 1.5-6.1) and have a greater motor impairment (OR 2.8, 95% CI 1.7-4.9). MPOC-56 subscale scores were not significantly associated with CAM use.

Conclusion: Physicians need to be aware of existing CAM therapies, the level of evidence supporting their efficacy (beneficence), their associated risks of adverse events (non-maleficence) and enable fair access to care that may be of benefit to each child.
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http://dx.doi.org/10.1017/cjn.2020.188DOI Listing
August 2020

Use of consensus methods to determine the early clinical signs of cerebral palsy.

Paediatr Child Health 2020 Aug 8;25(5):300-307. Epub 2019 May 8.

School of Physical and Occupational Therapy, McGill University, Montreal, Quebec.

Objectives: To develop expert-informed content regarding the early motor attributes of cerebral palsy (CP) that should prompt physician referral for diagnostic assessment of CP, as well as concurrent referral recommendations. This content will be used in the creation of knowledge translation (KT) tools for primary care practitioners and parents.

Methods: Two nominal group processes were conducted with relevant stakeholders, representing Canadian '' and ', using an integrated KT approach.

Results: Six attributes were identified that should prompt referral for diagnosis. If the child demonstrates: Early handedness <12 months; stiffness or tightness in the legs between 6 and 12 months; persistent fisting of the hands >4 months; persistent head-lag >4 months; inability to sit without support >9 months; any asymmetry in posture or movement. Five referral recommendations were agreed upon: Motor intervention specialist (physical therapy and/or occupational therapy) for ALL; speech-language pathology IF there is a communication delay; audiology IF there is parental or healthcare professional concern regarding a communication delay; functional vision specialist (e.g., optometrist or occupational therapist) IF there is a vision concern (e.g., not fixating, following, or tracking); feeding specialist (e.g., occupational therapist, speech-language pathologist) IF there are feeding difficulties (e.g., poor sucking, poor swallowing, choking, and/or not gaining weight).

Conclusion: Rigorous consensus methods provided the initial evidence necessary to inform the content of tools to assist primary care providers in the early detection of CP. Results will be validated through a Delphi process with international experts, and user-friendly formats of this KT tool will be developed collaboratively with stakeholders.
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http://dx.doi.org/10.1093/pch/pxz061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395325PMC
August 2020

A National Spinal Muscular Atrophy Registry for Real-World Evidence.

Can J Neurol Sci 2020 11 4;47(6):810-815. Epub 2020 Jun 4.

Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.

Background: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.

Methods: The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.

Results: The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.

Conclusion: Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
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http://dx.doi.org/10.1017/cjn.2020.111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656664PMC
November 2020

Congenital Malformations in Children With Cerebral Palsy: Is Prematurity Protective?

Pediatr Neurol 2020 07 12;108:70-76. Epub 2020 Feb 12.

Department of Pediatrics, McGill University, Montreal, Quebec City, Canada; Department of Neurology & Neurosurgery, McGill University, Montreal, Canada. Electronic address:

Background: Congenital malformations are more common in children who are born prematurely, and prematurity is the leading risk factor for cerebral palsy. The primary objective of this study was to describe the profile of congenital malformations in a Canadian cohort of children with cerebral palsy. The secondary objectives were to compare the profiles of children with cerebral palsy with and without a congenital malformation and explore the possible role of prematurity.

Methods: This retrospective cohort study utilized data from the Canadian Cerebral Palsy Registry, a population based registry of children with a confirmed diagnosis of cerebral palsy. Differences between groups were compared using Pearson's chi-square and Student t test as appropriate. Odds ratios and 95% confidence intervals were calculated RESULTS: Congenital malformations were present in 23% participants. In term-born children, brain malformations were the most common, whereas heart and gastrointestinal malformations were more common in children born prematurely. Children with a malformation had higher odds of being born at term (odds ratio 1.57, 95% confidence interval 1.20 to 2.04); having hypotonic, ataxic, or dyskinetic cerebral palsy (odds ratio 1.92, 95% confidence interval 1.35 to 2.72; being nonambulatory (odds ratio 1.70, 95% confidence interval 1.29 to 2.25); and having cerebral palsy-associated comorbidities.

Conclusions: One in four children with cerebral palsy have an associated congenital malformation. Their profile of term birth, higher Apgar scores, and lower frequency of perinatal seizures suggests a distinct causal pathway.
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http://dx.doi.org/10.1016/j.pediatrneurol.2020.02.002DOI Listing
July 2020

Ataxic-hypotonic cerebral palsy in a cerebral palsy registry: Insights into a distinct subtype.

Neurol Clin Pract 2020 Apr;10(2):131-139

Faculty of Medicine (JPL), McGill University, Montreal, QC; Department of Pediatrics and Neurology and Neurosurgery (MO, MS), McGill University, Montreal, QC; Centre for Outcomes Research and Evaluation (MO, PN, MS), Research Institute of the McGill University Health Centre, Montreal, QC; Department of Pediatrics (JA), University of Alberta, Edmonton, AB; Janeway Children's Hospital (DB), St. John's, NL; Department of Paediatrics (DF), University of Toronto, Bloorview Research Institute, Toronto, ON; Departments of Pediatrics and Clinical Neurosciences (AK), Cumming School of Medicine, University of Calgary, AB; Centre de réadaptation Marie Enfant du CHU Sainte-Justine (LK), Montreal, QC; Centre hospitalier universitaire de Sherbrooke (NP), Sherbrooke, QC; BC Children's Hospital (EvR), Vancouver, BC; and IWK Health Centre (EW), Halifax, NS, Canada.

Objective: To specifically report on ataxic-hypotonic cerebral palsy (CP) using registry data and to directly compare its features with other CP subtypes.

Methods: Data on prenatal, perinatal, and neonatal characteristics and gross motor function (Gross Motor Function Classification System [GMFCS]) and comorbidities in 35 children with ataxic-hypotonic CP were extracted from the Canadian Cerebral Palsy Registry and compared with 1,804 patients with other subtypes of CP.

Results: Perinatal adversity was detected significantly more frequently in other subtypes of CP (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.5-11.7). The gestational age at birth was higher in ataxic-hypotonic CP (median 39.0 weeks vs 37.0 weeks, = 0.027). Children with ataxic-hypotonic CP displayed more intrauterine growth restriction (OR 2.6, 95% CI 1.0-6.8) and congenital malformation (OR 2.4, 95% CI 1.2-4.8). MRI was more likely to be either normal (OR 3.8, 95% CI 1.4-10.5) or to show a cerebral malformation (OR 4.2, 95% CI 1.5-11.9) in ataxic-hypotonic CP. There was no significant difference in terms of GMFCS or the presence of comorbidities, except for more frequent communication impairment in ataxic-hypotonic CP (OR 4.2, 95% CI 1.5-11.6).

Conclusions: Our results suggest a predominantly genetic or prenatal etiology for ataxic-hypotonic CP and imply that a diagnosis of ataxic-hypotonic CP does not impart a worse prognosis with respect to comorbidities or functional impairment. This study contributes toward a better understanding of ataxic-hypotonic CP as a distinct nosologic entity within the spectrum of CP with its own pathogenesis, risk factors, clinical profile, and prognosis compared with other CP subtypes.
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http://dx.doi.org/10.1212/CPJ.0000000000000713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156190PMC
April 2020

Practice guideline: Treatment for insomnia and disrupted sleep behavior in children and adolescents with autism spectrum disorder: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

Neurology 2020 03 12;94(9):392-404. Epub 2020 Feb 12.

From the Pediatrics and Developmental Neuroscience Branch (A.W.B., T.G., R.K., A.T.), National Institute of Mental Health, NIH, Bethesda, MD; Department of Neurological Sciences (D.H.), University of Vermont Medical Center, Burlington; Department of Pediatric Neurology (M.O.), McGill University Health Centre, Montréal, Canada; Department of Neurology (M.J.A.), University of Florida College of Medicine, Gainesville; Developmental Pediatrics (A.B.), Our Special Kids Pediatric Care, Los Angeles, CA; Division of Developmental Medicine (C.B.) and Center for Pediatric Sleep Disorders (J.O.), Boston Children's Hospital, MA; Departments of Pediatrics and Psychiatry (D.C.), The Ohio State University College of Medicine, Columbus; Duke Center for Autism and Brain Development (G.D., L.S.), Duke University School of Medicine, Durham, NC; Northern Michigan Neurology (D.D.), Traverse City; Department of Child and Behavioral Sciences (R.L.F.), Johns Hopkins University, Baltimore, MD; Department of Neurology (D.G.), Charleston Area Medical Center, WV; Department of Neurology (G.G.), Kansas University Medical Center, Kansas City; American Academy of Neurology (S.M.), Minneapolis, MN; Division of Pediatric Neurology, Department of Pediatrics (D.M., S.A.), Loma Linda University School of Medicine, CA; Department of Clinical Neurosciences (T.P.), University of Calgary, Alberta, Canada; Department of Psychiatry and Behavioral Science and MIND Institute (A.S.), University of California, Davis; Division of Neurology (R.T.), Nicklaus Children's Hospital and Miami Children's Hospital, FL; Treatment and Research Institute for Autism Spectrum Disorders (Z.W.), Vanderbilt Kennedy Center, Nashville, TN; Autism Institute, College of Medicine (A.W.), Florida State University, Tallahassee; and Division of Neurology (M.W.), Rainbow Babies & Children's Hospital, Cleveland, OH.

Objective: To review pharmacologic and nonpharmacologic strategies for treating sleep disturbances in children and adolescents with autism spectrum disorder (ASD) and to develop recommendations for addressing sleep disturbance in this population.

Methods: The guideline panel followed the American Academy of Neurology 2011 guideline development process, as amended. The systematic review included studies through December 2017. Recommendations were based on evidence, related evidence, principles of care, and inferences.

Major Recommendations Level B: For children and adolescents with ASD and sleep disturbance, clinicians should assess for medications and coexisting conditions that could contribute to the sleep disturbance and should address identified issues. Clinicians should counsel parents regarding strategies for improved sleep habits with behavioral strategies as a first-line treatment approach for sleep disturbance either alone or in combination with pharmacologic or nutraceutical approaches. Clinicians should offer melatonin if behavioral strategies have not been helpful and contributing coexisting conditions and use of concomitant medications have been addressed, starting with a low dose. Clinicians should recommend using pharmaceutical-grade melatonin if available. Clinicians should counsel children, adolescents, and parents regarding potential adverse effects of melatonin use and the lack of long-term safety data. Clinicians should counsel that there is currently no evidence to support the routine use of weighted blankets or specialized mattress technology for improving disrupted sleep. If asked about weighted blankets, clinicians should counsel that the trial reported no serious adverse events with blanket use and that blankets could be a reasonable nonpharmacologic approach for some individuals.
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http://dx.doi.org/10.1212/WNL.0000000000009033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238942PMC
March 2020

Cerebral palsy in Canada, 2011-2031: results of a microsimulation modelling study of epidemiological and cost impacts.

Health Promot Chronic Dis Prev Can 2020 Feb;40(2):25-37

Population Health Surveillance and Epidemiology, Office of the Provincial Health Officer, British Columbia Ministry of Health, Victoria, British Columbia, Canada.

Introduction: The objective of our study was to present model-based estimates and projections on current and future health and economic impacts of cerebral palsy in Canada over a 20-year time horizon (2011-2031).

Methods: We used Statistics Canada's Population Health Model (POHEM)-Neurological to simulate individuals' disease states, risk factors and health determinants and to describe and project health outcomes, including disease incidence, prevalence, life expectancy, health-adjusted life expectancy, health-related quality of life and health care costs over the life cycle of Canadians. Cerebral palsy cases were identified from British Columbia's health administrative data sources. A population-based cohort was then used to generate the incidence and mortality rates, enabling the projection of future incidence and mortality rates. A utility-based measure (Health Utilities Index Mark 3) was also included in the model to reflect various states of functional health to allow projections of health-related quality of life. Finally, we estimated caregiving parameters and health care costs from Canadian national surveys and health administrative data and included them as model parameters to assess the health and economic impact of cerebral palsy.

Results: Although the overall crude incidence rate of cerebral palsy is projected to remain stable, newly diagnosed cases of cerebral palsy will rise from approximately 1800 in 2011 to nearly 2200 in 2031. In addition, the number of people with the condition is expected to increase from more than 75 000 in 2011 to more than 94 000 in 2031. Direct health care costs in constant 2010 Canadian dollars were about $11 700 for children with cerebral palsy aged 1-4 years versus about $600 for those without the condition. In addition, people with cerebral palsy tend to have longer periods in poorer health-related quality of life.

Conclusion: Individuals with cerebral palsy will continue to face challenges related to an ongoing need for specialized medical care and a rising need for supportive services. Our study offers important insights into future costs and impacts associated with cerebral palsy and provides valuable information that could be used to develop targeted health programs and strategies for Canadians living with this condition.
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http://dx.doi.org/10.24095/hpcdp.40.2.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053851PMC
February 2020

Seizures in Epilepsy With Eyelid Myoclonia May Be Provoked by Eye Closure, Not Fixation Removal.

Pediatr Neurol 2020 04 19;105:62-64. Epub 2019 Oct 19.

Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada.

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http://dx.doi.org/10.1016/j.pediatrneurol.2019.10.001DOI Listing
April 2020

Current Referral Practices for Diagnosis and Intervention for Children with Cerebral Palsy: A National Environmental Scan.

J Pediatr 2020 01;216:173-180.e1

School of Physical and Occupational Therapy, McGill University, Montreal, Quebec, Canada; Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal, Montreal, Quebec, Canada; Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. Electronic address:

Objectives: To describe current physician referral practices with respect to age at referral to medical specialists for initial diagnosis of cerebral palsy (CP) and rehabilitation specialists for intervention and to identify factors associated with delayed referral.

Study Design: National environmental scan of 455 children diagnosed with CP who were born in Canada between 2008 and 2011, selected from 4 sites within the Canadian CP Registry (Edmonton, Calgary, Toronto, and Montreal). Two sources of information were used-children's medical charts and the population-based registry, which provided corresponding data for each child. Primary outcomes extracted from the charts were age at referral for diagnostic assessment, age at diagnosis, age at referral for rehabilitation services, and age at initial rehabilitation intervention. Twelve variables were explored as potential predictors. Descriptive statistics, bivariate analyses, and multiple linear regressions were conducted.

Results: Median age (in months) at referral for diagnostic assessment was 8 (mean: 12.7 ± 14.3), diagnosis 16 (mean: 18.9 ± 12.8), referral for rehabilitation services 10 (mean: 13.4 ± 13.5), and rehabilitation initiation 12 (mean: 15.9 ± 12.9). Lower maternal education, mild severity of motor dysfunction, type of CP, early discharge after birth, and region of residence explained between 20% and 32% of the variance in age at referral for assessment, diagnosis, referral for rehabilitation, and rehabilitation initiation.

Conclusions: Findings suggest wide variability exists in the age at which young children with CP are referred to specialists for diagnosis and intervention. User-friendly tools are therefore needed to enhance early detection and referral strategies by primary care practitioners, to ensure early interventions to optimize developmental outcomes and enhance opportunities for neural repair at a younger age.
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http://dx.doi.org/10.1016/j.jpeds.2019.09.035DOI Listing
January 2020

Behavioral difficulties, sleep problems, and nighttime pain in children with cerebral palsy.

Res Dev Disabil 2019 Dec 17;95:103500. Epub 2019 Oct 17.

Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada; Research Institute, McGill University Health Centre, Montreal, Quebec, Canada. Electronic address:

Background: Children with cerebral palsy (CP) may be at risk of behavioral difficulties.

Aims: 1) Determine the prevalence of behavioral difficulties in preschool- and school-aged children with CP and 2) Assess the association between behavioral difficulties and a) sleep problems, b) nighttime pain and c) child characteristics (age, CP phenotype, comorbidities).

Methods And Procedures: Caregivers of 113 children with CP aged 4-12 years [mean (SD) age = 7.4 (2.5) years; 61.9% male] completed the Strengths and Difficulties Questionnaire, Sleep Disturbance Scale for Children and a sleep quality questionnaire to assess child behavior, sleep and nighttime pain, respectively.

Outcomes And Results: 25.6% of children (17.6% preschool-aged; 29.1% school-aged) had behavioral difficulties. Sleep problems (odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4-24.4) and nighttime pain (OR 4.1, 95% CI 1.5-11.5) were associated with behavioral difficulties. Sleep problems remained significantly associated with behavioral difficulties (adjusted OR 7.5, 95% CI 2.6-21.4) when adjusted for nighttime pain, age and non-ambulatory status.

Conclusions And Implications: Behavioral difficulties were reported in one in four children with CP and were associated with sleep problems and nighttime pain. Identifying and treating behavioral difficulties, sleep problems or nighttime pain is important in the care of children with CP.
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http://dx.doi.org/10.1016/j.ridd.2019.103500DOI Listing
December 2019

Practice guideline update summary: Acute treatment of migraine in children and adolescents: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

Headache 2019 09;59(8):1158-1173

Department of Neurology, Mayo Clinic, Rochester, MN.

Objective: To provide evidence-based recommendations for the acute symptomatic treatment of children and adolescents with migraine.

Methods: We performed a systematic review of the literature and rated risk of bias of included studies according to the American Academy of Neurology classification of evidence criteria. A multidisciplinary panel developed practice recommendations, integrating findings from the systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence.

Results: There is evidence to support the efficacy of the use of ibuprofen, acetaminophen (in children and adolescents), and triptans (mainly in adolescents) for the relief of migraine pain, although confidence in the evidence varies between agents. There is high confidence that adolescents receiving oral sumatriptan/naproxen and zolmitriptan nasal spray are more likely to be headache free at 2 hours than those receiving placebo. No acute treatments were effective for migraine-related nausea or vomiting; some triptans were effective for migraine-related phonophobia and photophobia.

Recommendations: Recommendations for the treatment of acute migraine in children and adolescents focus on the importance of early treatment, choosing the route of administration best suited to the characteristics of the individual migraine attack, and providing counselling on lifestyle factors that can exacerbate migraine, including trigger avoidance and medication overuse.
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http://dx.doi.org/10.1111/head.13628DOI Listing
September 2019

Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

Headache 2019 09;59(8):1144-1157

Division of Behavioral Medicine & Clinical Psychology, Cincinnati Children's Hospital Medical Center, OH.

Objective: To provide updated evidence-based recommendations for migraine prevention using pharmacologic treatment with or without cognitive behavioral therapy in the pediatric population.

Methods: The authors systematically reviewed literature from January 2003 to August 2017 and developed practice recommendations using the American Academy of Neurology 2011 process, as amended.

Results: Fifteen class I-III studies on migraine prevention in children in adolescents met inclusion criteria. There is insufficient evidence to determine if children and adolescents receiving divalproex, onabotulinumtoxinA, amitriptyline, nimodipine and flunarizine are more or less likely than those receiving placebo to have a reduction in headache frequency. Children with migraine receiving propranolol are possibly more likely than those receiving placebo to have an at least 50% reduction in headache frequency. Children and adolescents receiving topiramate and cinnarizine are probably more likely than those receiving placebo to have a decrease in headache frequency. Children with migraine receiving amitriptyline plus cognitive behavioral therapy are more likely than those receiving amitriptyline plus headache education to have a reduction in headache frequency. Recommendations The majority of randomized controlled trials studying the efficacy of preventive medications for pediatric migraine fail to demonstrate superiority to placebo. Recommendations for the prevention of migraine in children include counseling on lifestyle and behavioral factors that influence headache frequency, and assessment and management of comorbid disorders associated with headache persistence. Clinicians should engage in shared decision making with patients and caregivers regarding the use of preventive treatments for migraine, including discussion of the limitations in the evidence to support pharmacologic treatments.
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http://dx.doi.org/10.1111/head.13625DOI Listing
September 2019

Practice guideline update summary: Acute treatment of migraine in children and adolescents: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

Neurology 2019 09 14;93(11):487-499. Epub 2019 Aug 14.

From the Departments of Pediatrics and Neurology/Neurosurgery (M.O.), McGill University, Montréal, Canada; Departments of Clinical Neurosciences, Psychiatry, Pediatrics, and Community Health Sciences (T.P.), Cumming School of Medicine, University of Calgary, Canada; Department of Pediatrics (Neurology) (Y.-H.M.), Northwestern University Feinberg School of Medicine, Chicago, IL; Neurology Department (S.P.), Southern California Permanente Medical Group, Kaiser, Los Angeles; Division of Neurology (L.B.), Children's Hospital of Philadelphia, PA; Department of Neurology (D.G.), Charleston Area Medical Center, WV; Division of Neurology (A.D.H.), Cincinnati Children's Hospital Medical Center, OH; Department of Neuroscience and Spine (N.L.), St. Anthony Hospital-Centura Health, Lakewood, CO; University of Louisville Comprehensive Headache Program and University of Louisville Child Neurology Residency Program (M.S.), KY; Division of Neurology, NeuroDevelopmental Science Center (M.C.V.), Akron Children's Hospital, OH; Rochester (E.M.G.), NY; St. Paul (E.L.), MN; O'Fallon (H.Z.), MO; Division of Neurology (M.Y.), Children's Hospital Colorado, Aurora; and Department of Neurology (K.M.), Mayo Clinic, Rochester, MN.

Objective: To provide evidence-based recommendations for the acute symptomatic treatment of children and adolescents with migraine.

Methods: We performed a systematic review of the literature and rated risk of bias of included studies according to the American Academy of Neurology classification of evidence criteria. A multidisciplinary panel developed practice recommendations, integrating findings from the systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence.

Results: There is evidence to support the efficacy of the use of ibuprofen, acetaminophen (in children and adolescents), and triptans (mainly in adolescents) for the relief of migraine pain, although confidence in the evidence varies between agents. There is high confidence that adolescents receiving oral sumatriptan/naproxen and zolmitriptan nasal spray are more likely to be headache-free at 2 hours than those receiving placebo. No acute treatments were effective for migraine-related nausea or vomiting; some triptans were effective for migraine-related phonophobia and photophobia.

Recommendations: Recommendations for the treatment of acute migraine in children and adolescents focus on the importance of early treatment, choosing the route of administration best suited to the characteristics of the individual migraine attack, and providing counseling on lifestyle factors that can exacerbate migraine, including trigger avoidance and medication overuse.
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http://dx.doi.org/10.1212/WNL.0000000000008095DOI Listing
September 2019

Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society.

Neurology 2019 09 14;93(11):500-509. Epub 2019 Aug 14.

From the Departments of Pediatrics and Neurology/Neurosurgery (M.O.), McGill University, Montréal, Canada; Departments of Clinical Neurosciences, Psychiatry, Pediatrics, and Community Health Sciences (T.P.), Cumming School of Medicine, University of Calgary, Canada; Division of Neurology (L.B.), Children's Hospital of Philadelphia, PA; Neurology Department (S.P.), Southern California Permanente Medical Group, Kaiser Los Angeles; Rochester (E.M.G.), NY; Department of Neurology (D.G.), Charleston Area Medical Center, Charleston, WV; Department of Pediatrics (Neurology) (Y.H.-M.), Northwestern University Feinberg School of Medicine, Chicago, IL; St. Paul (E.L.), MN; Department of Neuroscience and Spine (N.L.), St. Anthony Hospital-Centura Health, Lakewood, CO; Department of Neurology (K.M.), Mayo Clinic, Rochester, MN; Division of Behavioral Medicine & Clinical Psychology (S.W.P., A.D.H.), Cincinnati Children's Hospital Medical Center, OH; University of Louisville Comprehensive Headache Program and University of Louisville Child Neurology Residency Program (M.S.), KY; Division of Neurology (M.C.V.), NeuroDevelopmental Science Center, Akron Children's Hospital, OH; Division of Neurology (M.Y.), Children's Hospital Colorado, Aurora; and O'Fallon (H.Z.), MO.

Objective: To provide updated evidence-based recommendations for migraine prevention using pharmacologic treatment with or without cognitive behavioral therapy in the pediatric population.

Methods: The authors systematically reviewed literature from January 2003 to August 2017 and developed practice recommendations using the American Academy of Neurology 2011 process, as amended.

Results: Fifteen Class I-III studies on migraine prevention in children and adolescents met inclusion criteria. There is insufficient evidence to determine if children and adolescents receiving divalproex, onabotulinumtoxinA, amitriptyline, nimodipine, or flunarizine are more or less likely than those receiving placebo to have a reduction in headache frequency. Children with migraine receiving propranolol are possibly more likely than those receiving placebo to have an at least 50% reduction in headache frequency. Children and adolescents receiving topiramate and cinnarizine are probably more likely than those receiving placebo to have a decrease in headache frequency. Children with migraine receiving amitriptyline plus cognitive behavioral therapy are more likely than those receiving amitriptyline plus headache education to have a reduction in headache frequency.

Recommendations: The majority of randomized controlled trials studying the efficacy of preventive medications for pediatric migraine fail to demonstrate superiority to placebo. Recommendations for the prevention of migraine in children include counseling on lifestyle and behavioral factors that influence headache frequency and assessment and management of comorbid disorders associated with headache persistence. Clinicians should engage in shared decision-making with patients and caregivers regarding the use of preventive treatments for migraine, including discussion of the limitations in the evidence to support pharmacologic treatments.
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http://dx.doi.org/10.1212/WNL.0000000000008105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746206PMC
September 2019

Losing a diagnosis of cerebral palsy: a comparison of variables at 2 and 5 years.

Dev Med Child Neurol 2020 01 4;62(1):83-88. Epub 2019 Jul 4.

Department of Pediatrics, McGill University, Montreal, Quebec, Canada.

Aim: This study aims to identify characteristics at 2 years of age that differ between children with confirmed cerebral palsy (CP) and a non-CP diagnosis by 5 years of age.

Method: This was a retrospective cohort analysis. A CP diagnosis may be considered a 'probable' diagnosis at 2 years, which is often 'confirmed' at 4 or 5 years, particularly in the context of CP registries. A total of 1683 children with a diagnosis of CP or probable CP at 2 years of age were identified from the Canadian Cerebral Palsy Registry, of whom 48 received a non-CP diagnosis at 5 years ('non-confirmed CP'). Perinatal adversity, preterm birth status, Gross Motor Function Classification System (GMFCS) level, presence of comorbidities, magnetic resonance imaging (MRI) findings, and initial CP motor type were compared between the two groups by univariate and logistic regression analyses.

Results: χ analysis and multivariate analysis both confirmed that children with a non-CP diagnosis by 5 years of age were more likely to have a normal MRI (χ odds ratio [OR]=7.8, 95% confidence interval [CI]=3.8-16.1; OR=5.4, 95% CI=2.4-12.5), ataxic-hypotonic (χ OR=10.1, 95% CI=4.9-21.2; OR=6.1, 95% CI=2.2-16.2) or dyskinetic CP (χ OR=2.7, 95% CI=1.2-5.9; OR=2.9, 95% CI=1.0-7.6), born at term (χ OR=3.7, 95% CI=1.7-8.0; OR=3.6, 95% CI=1.0-12.1), and lack perinatal adversity (χ OR=4.1, 95% CI=1.6-10.7; OR=3.4, 95% CI=1.0-11.7).

Interpretation: Normal MRI, ataxic-hypotonic or dyskinetic CP, lack of perinatal adversity, and term birth are associated with a higher odds of non-CP diagnosis by 5 years of age, thus potentially enhancing diagnostic work-up.

What This Paper Adds: Normal magnetic resonance imaging (MRI) at 2 years was associated with a non-cerebral palsy (CP) diagnosis by 5 years. Diagnosis of ataxic-hypotonic or dyskinetic CP motor subtype at 2 years was associated with a non-CP diagnosis by 5 years. Perinatal adversity and preterm birth were rarer with a non-CP diagnosis by 5 years.
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http://dx.doi.org/10.1111/dmcn.14309DOI Listing
January 2020

Neurofilament as a potential biomarker for spinal muscular atrophy.

Ann Clin Transl Neurol 2019 May 17;6(5):932-944. Epub 2019 Apr 17.

Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland.

Objective: To evaluate plasma phosphorylated neurofilament heavy chain (pNF-H) as a biomarker in spinal muscular atrophy (SMA).

Methods: Levels of pNF-H were measured using the ProteinSimple platform in plasma samples from infants with SMA enrolled in ENDEAR (NCT02193074) and infants/children without neurological disease.

Results: Median pNF-H plasma level was 167.0 pg/mL (7.46-7,030; n = 34) in children without SMA (aged 7 weeks-18 years) and was higher in those aged < 1 versus 1-18 years (0.0002). In ENDEAR participants with infantile-onset SMA, median baseline pNF-H level (15,400 pg/mL; 2390-50,100;  = 117) was ~10-fold higher than that of age-matched infants without SMA (<0.0001) and ~90-fold higher than children without SMA (<0.0001). Higher pretreatment pNF-H levels in infants with SMA were associated with younger age at symptom onset, diagnosis, and first dose; lower baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders score; and lower peroneal compound muscle potential amplitude. Nusinersen treatment was associated with a rapid and greater decline in pNF-H levels: nusinersen-treated infants experienced a steep 71.9% decline at 2 months to 90.1% decline at 10 months; sham control-treated infants declined steadily by 16.2% at 2 months and 60.3% at 10 months.

Interpretation: Plasma pNF-H levels are elevated in infants with SMA. Levels inversely correlate with age at first dose and several markers of disease severity. Nusinersen treatment is associated with a significant decline in pNF-H levels followed by relative stabilization. Together these data suggest plasma pNF-H is a promising marker of disease activity/treatment response in infants with SMA.
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http://dx.doi.org/10.1002/acn3.779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530526PMC
May 2019

Profile of children with cerebral palsy spectrum disorder and a normal MRI study.

Neurology 2019 07 24;93(1):e88-e96. Epub 2019 May 24.

From the Faculty of Medicine (A.S.) and Departments of Pediatrics (M.O., M.S.) and Neurology & Neurosurgery (M.O., M.S.), McGill University; Canadian Cerebral Palsy Registry (S.D.H.), Research Institute of the McGill University Health Centre, Montreal; Department of Pediatrics (J.A.), University of Alberta, Edmonton; Janeway Children's Hospital (D.B.), St. John's; Department of Paediatrics (D.F.), Bloorview Research Institute, University of Toronto; Departments of Pediatrics and Clinical Neurosciences (A.K.), Cumming School of Medicine, University of Calgary; Centre de Réadaptation Marie Enfant du CHU Sainte-Justine (L.K.), Montreal; Centre Hospitalier Universitaire de Sherbrooke (N.P.); BC Children's Hospital (E.V.R.), Vancouver; and IWK Health Centre (E.W.), Halifax, Canada.

Objective: This study looks at what profile can be expected in children with cerebral palsy spectrum disorder (CP) and a normal MRI.

Methods: The data were excerpted from the Canadian Cerebral Palsy Registry database. Only patients who had undergone MRI were included in the analysis. Neuroimaging classification was ascertained by university-based pediatric neuroradiologists and split into 2 categories: normal and abnormal MRIs. Six factors were then compared between those 2 groups: prematurity, perinatal adversity, presence of more than 1 comorbidity, CP subtype, bimanual dexterity (Manual Ability Classification System [MACS]), and gross motor function (Gross Motor Function Classification System [GMFCS]).

Results: Participants with no perinatal adversity were 5.518 times more likely to have a normal MRI ( < 0.0001, 95% confidence interval [CI] 4.153-7.330). Furthermore, participants with dyskinetic, ataxic/hypotonic, and spastic diplegic forms of CP were 2.045 times more likely to have a normal MRI than those with hemiplegia, triplegia, and quadriplegia ( < 0.0001, 95% CI 1.506-2.778). No significant difference was found in prematurity, GMFCS levels, MACS levels, and the number of comorbidities.

Conclusions: Normal MRIs were associated with lack of perinatal adversity as well as with the dyskinetic, ataxic/hypotonic, and spastic diplegic CP subtypes. As MRI normality is not strongly associated with the severity of CP, continuous follow-up in children with normal imaging appears warranted. Further advanced imaging modalities, as well as strong consideration for metabolic and genetic testing, may provide additional insights into causal pathways in this population.
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http://dx.doi.org/10.1212/WNL.0000000000007726DOI Listing
July 2019

Is Cerebral Palsy Changing in High Resource Settings? Data From the Quebec Cerebral Palsy Registry.

J Child Neurol 2019 09 10;34(10):567-573. Epub 2019 May 10.

1 Department of Pediatrics, McGill University, Montreal, Québec, Canada.

Advances in maternal and perinatal care in developed countries have led to improved health outcomes for children. These changes may have impacted the profile of children with a cerebral palsy (CP) and groups at risk for CP over time. Using data from the Canadian CP Registry, the objectives of this retrospective cohort study were to describe the profile of children with CP in Quebec born between 1999 and 2010 and identify possible temporal variation in CP risk factors and phenotypic profile. Our sample consisted of 662 children with CP in Quebec. No change in profile or associated risk factors was observed across the birth cohorts 1999 to 2010. Prematurity remains the largest risk factor for CP in Quebec, and children with CP have multiple comorbidities that contribute to overall CP burden. CP registries offer a unique platform to study spectrum disorders and their longitudinal changes over time.
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http://dx.doi.org/10.1177/0883073819845272DOI Listing
September 2019

Comprehensive systematic review summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders.

Neurology 2019 05;92(19):907-915

From the Department of Clinical Neurosciences, Psychiatry, Pediatrics and Community Health Sciences (T.P., D.M.), Cumming School of Medicine, University of Calgary, Alberta, Canada; Department of Pediatrics (Neurology) (Y.H.-M.), Northwestern University Feinberg School of Medicine, Chicago, IL; Departments of Neurology and Neurosurgery (M.S.O.), Fixel Center for Neurological Diseases, University of Florida, Gainesville; Department of Neurology (J.J.), Baylor College of Medicine, Houston, TX; Department of Psychiatry and Biobehavioral Sciences (J.P.), Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles; Department of Neuropsychiatry (A.E.C.), BSMHFT, University of Birmingham and Aston University, UK; Department of Psychiatry, Social Psychiatry, and Psychotherapy (K.M.-V.), Hannover Medical School, Germany; Department of Psychology (D.W.W.), Marquette University, Milwaukee, WI; Massachusetts Chapter (M.R.), Tourette Association of America, Bayside, NY; Waisman Center (E.J.), University Center for Excellence in Developmental Disabilities, University of Wisconsin, Madison; Technische Universitaet Dresden (V.R.), Germany; and Departments of Pediatric and Neurology/Neurosurgery (M.O.), McGill University, Montréal, Canada.

Objective: To systematically evaluate the efficacy of treatments for tics and the risks associated with their use.

Methods: This project followed the methodologies outlined in the 2011 edition of the American Academy of Neurology's guideline development process manual. We included systematic reviews and randomized controlled trials on the treatment of tics that included at least 20 participants (10 participants if a crossover trial), except for neurostimulation trials, for which no minimum sample size was required. To obtain additional information on drug safety, we included cohort studies or case series that specifically evaluated adverse drug effects in individuals with tics.

Results: There was high confidence that the Comprehensive Behavioral Intervention for Tics was more likely than psychoeducation and supportive therapy to reduce tics. There was moderate confidence that haloperidol, risperidone, aripiprazole, tiapride, clonidine, onabotulinumtoxinA injections, 5-ling granule, Ningdong granule, and deep brain stimulation of the globus pallidus were probably more likely than placebo to reduce tics. There was low confidence that pimozide, ziprasidone, metoclopramide, guanfacine, topiramate, and tetrahydrocannabinol were possibly more likely than placebo to reduce tics. Evidence of harm associated with various treatments was also demonstrated, including weight gain, drug-induced movement disorders, elevated prolactin levels, sedation, and effects on heart rate, blood pressure, and ECGs.

Conclusions: There is evidence to support the efficacy of various medical, behavioral, and neurostimulation interventions for the treatment of tics. Both the efficacy and harms associated with interventions must be considered in making treatment recommendations.
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http://dx.doi.org/10.1212/WNL.0000000000007467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537130PMC
May 2019