External ventricular drainage in the management of pediatric patients with posterior fossa tumors and hydrocephalus: a retrospective cohort study.

PURPOSE: To determine whether intraoperative adjunctive EVD placement in patients with a posterior fossa tumor (PFT) led to improved surgical, radiographic, and clinical outcomes compared to those who did not receive an EVD. METHODS: Patients were grouped as those who underwent routine intraoperative adjunctive EVD insertion and those who did not at time of PFT resection. Patients who pre-operatively required a clinically indicated EVD insertion were excluded. Comparative analyses between both groups were conducted to evaluate clinical, radiological, and pathological outcomes. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were computed for post-operative outcomes. RESULTS: Fifty-five selected patients were included, 15 who had an EVD placed at the time of PFT resection surgery, and 40 who did not. Children without an EVD did not experience a higher rate of complications or poorer post-operative outcomes compared to those with an EVD placed during resection surgery. There was no significant difference in the degree of gross total resection (p = 0.129), post-operative CSF leak (p = 1.000), and post-operative hemorrhage (p = 0.554) between those with an EVD and those without. The frequency of new cranial nerve deficits post-operatively was higher in those with an EVD (40%) compared to those without (3%, p = 0.001). There was a trend towards more frequently observed post-operative hydrocephalus in the EVD group (p = 0.057). CONCLUSION: The routine use of EVD as an intraoperative adjunct in clinically stable pediatric patients with posterior fossa tumors and hydrocephalus may not be associated with improved radiological or clinical outcomes.

Transradial versus transfemoral access for mechanical thrombectomy in acute ischemic stroke: A retrospective cohort study.

BACKGROUND: The objective of this study was to compare procedural and clinical outcomes in patients with acute ischemic stroke (AIS) treated via transradial access (TRA) mechanical thrombectomy (MT) versus conventional transfemoral access (TFA). METHODS: We performed a retrospective analysis of consecutive patients with AIS treated with TRA versus TFA MT at our tertiary comprehensive stroke center. Access choice was individualized based on occlusion site, aortic and arch anatomy. Outcomes were extracted from our institutional stroke registry and included procedural time, Thrombolysis in Cerebral Infarction (TICI) reperfusion score, NIHSS, 90-day mRS and 90-day mortality. Comparisons were performed using Student t-Test and Fischer's exact test as appropriate. RESULTS: 175 mechanical thrombectomies were performed during the study interval; 39 (22%) were performed via TRA and 136 (79%) TFA. Access to reperfusion time was 36.3 ± 24.5 minutes in the TRA group and 21.9 ± 17.6 in the TFA group (p<0.001). The proportion of patients with a TICI reperfusion score of 2b or 3 was similar in both groups (TRA: 34 (87%) vs. TFA: 121 (89%) p=0.559. The median 90-day mRS was similar between both groups (p=0.170), as was the 90-day mortality (p = 0.509). CONCLUSIONS: While TFA is faster in our cohort, TFA and TRA are both safe and effective for MT in acute ischemic stroke. While TFA remains mainstay, TRA can be valuable in variant anatomy despite its technical limitations. Individualizing access based on advanced imaging and patient factors may improve practice; however, updates in catheter and access technology are necessary to optimize outcomes with TRA.

Cognitive and Behavioral Functioning in Childhood Acquired Demyelinating Syndromes.

OBJECTIVES: The aim of this study was to describe cognitive, academic, and psychosocial outcomes after an incident demyelinating event (acquired demyelinating syndromes, ADS) in childhood and to investigate the contribution of brain lesions and confirmed MS diagnosis on outcome. METHODS: Thirty-six patients with ADS (mean age=12.2 years, SD=2.7, range: 7-16 years) underwent brain MRI scans at presentation and at 6-months follow-up. T2-weighted lesions on MRI were assessed using a binary classification. At 6-months follow-up, patients underwent neuropsychological evaluation and were compared with 42 healthy controls. RESULTS: Cognitive, academic, and behavioral outcomes did not differ between the patients with ADS and controls. Three of 36 patients (8.3%) were identified with cognitive impairment, as determined by performance falling ≤1.5 SD below normative values on more than four independent tests in the battery. Poor performance on a visuomotor integration task was most common, observed among 6/32 patients, but this did not differ significantly from controls. Twelve of 36 patients received a diagnosis of MS within 3 years post-ADS. Patients with MS did not differ from children with monophasic ADS in terms of cognitive performance at the 6-months follow-up. Fatigue symptoms were reported in 50% of patients, irrespective of MS diagnosis. Presence of brain lesions at onset and 6 months post-incident demyelinating event did not associate with cognitive outcome. CONCLUSIONS: Children with ADS experience a favorable short-term neurocognitive outcome, even those confirmed to have MS. Longitudinal evaluations of children with monophasic ADS and MS are required to determine the possibility of late-emerging sequelae and their time course. (JINS, 2016, 22, 1050-1060).

Aspiration tubing diameter is a key determinant of vacuum pressure and is associated with procedural outcome in mechanical thrombectomy for large vessel occlusion: An experimental and cohort study.

BACKGROUND: We (1) evaluated the effect of aspiration tubing diameter on intraluminal pressure and (2) compared thrombectomy outcomes in patients treated using small diameter tubing versus those treated using large diameter vacuum tubing. METHODS: Intraluminal negative pressure was measured in a validated benchtop set up where consistency of negative pressure (inHg) was measured between static and dynamic aspiration. Static aspiration refers to activation of vacuum once the catheter is engaged with the clot. Dynamic aspiration refers to activation of vacuum when the catheter is slightly proximal to the clot. Four different sizes of vacuum tubing were trialed. We performed a retrospective analysis of consecutive patients who underwent mechanical thrombectomy. Procedural and functional outcomes were compared. RESULTS: The large diameter aspiration tubing held a consistent high negative pressure in static and dynamic aspiration (p = 0.152). Tubing types I to III were associated with a significant fall off in negative pressure between static and dynamic technique (p < 0.05). Two-hundred and five patients were included in the retrospective analysis; 124 (60%) underwent thrombectomy using small diameter vacuum tubing, and 81 (40%) using the large tubing. Mean thrombectomy time was shorter with the larger tubing [25.9 (17.9) minutes] versus the small tubing [37.5 (28.5) minutes, p = 0.002]. A greater proportion of patients had a thrombolysis in cerebral infarction score ≥2b in the group treated using the large tubing (78, 99%) than those with the small tubing (96, 78%, p < 0.001). CONCLUSION: Vacuum tubing diameter is linearly associated with intraluminal aspiration pressure. These findings have clinical significance as shown by increased recanalization rates and decreased thrombectomy times when large-diameter aspiration tubing is used. Shifting the paradigm toward a flow-based technique using large-bore vacuum tubing ought to be considered.

A re-evaluation of the Endoscopic Third Ventriculostomy Success Score: a Hydrocephalus Clinical Research Network study.

OBJECTIVE: The Hydrocephalus Clinical Research Network (HCRN) conducted a prospective study 1) to determine if a new, better-performing version of the Endoscopic Third Ventriculostomy Success Score (ETVSS) could be developed, 2) to explore the performance characteristics of the original ETVSS in a modern endoscopic third ventriculostomy (ETV) cohort, and 3) to determine if the addition of radiological variables to the ETVSS improved its predictive abilities. METHODS: From April 2008 to August 2019, children (corrected age ≤ 17.5 years) who underwent a first-time ETV for hydrocephalus were included in a prospective multicenter HCRN study. All children had at least 6 months of clinical follow-up and were followed since the index ETV in the HCRN Core Data Registry. Children who underwent choroid plexus cauterization were excluded. Outcome (ETV success) was defined as the lack of ETV failure within 6 months of the index procedure. Kaplan-Meier curves were constructed to evaluate time-dependent variables. Multivariable binary logistic models were built to evaluate predictors of ETV success. Model performance was evaluated with Hosmer-Lemeshow and Harrell's C statistics. RESULTS: Seven hundred sixty-one children underwent a first-time ETV. The rate of 6-month ETV success was 76%. The Hosmer-Lemeshow and Harrell's C statistics of the logistic model containing more granular age and etiology categorizations did not differ significantly from a model containing the ETVSS categories. In children ≥ 12 months of age with ETVSSs of 50 or 60, the original ETVSS underestimated success, but this analysis was limited by a small sample size. Fronto-occipital horn ratio (p = 0.37), maximum width of the third ventricle (p = 0.39), and downward concavity of the floor of the third ventricle (p = 0.63) did not predict ETV success. A possible association between the degree of prepontine adhesions on preoperative MRI and ETV success was detected, but this did not reach statistical significance. CONCLUSIONS: This modern, multicenter study of ETV success shows that the original ETVSS continues to demonstrate good predictive ability, which was not substantially improved with a new success score. There might be an association between preoperative prepontine adhesions and ETV success, and this needs to be evaluated in a future large prospective study.

2010 McDonald criteria for diagnosing pediatric multiple sclerosis.

OBJECTIVE: The diagnosis of multiple sclerosis (MS) rests on confirmation of central nervous system inflammatory disease that is disseminated in space and time, as evidenced clinically or by magnetic resonance imaging (MRI). The 2010 McDonald criteria simplified MRI requirements, and newly proposed that the criteria are also suitable for the diagnosis of pediatric MS. METHODS: In a national prospective incident cohort study of children with acute demyelination observed for a minimum of 24 months, baseline and serial clinical and MRI examinations were used to retrospectively evaluate the 2010 and 2005 McDonald criteria using clinically relapsing disease as the gold standard. RESULTS: Of 212 eligible participants, 34 experienced 2 or more clinical attacks, 58 met the 2010 criteria, and 42 met 2005 McDonald criteria. The 2010 criteria demonstrated high sensitivity (100%), specificity (86%), positive predictive value (76%), and negative predictive value (100%) for children older than 11 years with non-acute disseminated encephalomyelitis (ADEM) presentations, as did the 2005 McDonald criteria. In younger children with a non-ADEM presentation, PPV of the 2010 criteria was only 55%. None of the 50 children with ADEM met clinical criteria for MS, but 10 met 2010 and 4 met 2005 criteria. INTERPRETATION: Both 2005 and 2010 McDonald criteria identify children with relapsing-remitting MS, although caution is suggested when applying these criteria in younger children. The 2010 McDonald criteria are simple and enable an early diagnosis of MS, but are not suited for application in the context of ADEM-like presentations.

Age-related variables in childhood epilepsy: how do they relate to each other and to quality of life?

How do age of onset and duration of epilepsy correlate with each other and with patient-reported outcomes? To address this question, we explored whether age of onset, duration, and proportion of life with epilepsy are either similar or relatively independent variables that can be used as markers on how children experience the complexity of epilepsy and adjustment. Three hundred ninety-one Canadian and 266 Hong Kong youth with epilepsy completed the childhood epilepsy-specific quality of life (QOL) measure (CHEQOL-25). Each cohort was separately stratified by tertiles for age of onset, life proportion with epilepsy, and duration of epilepsy. Pearson's r was used for correlation analysis. The epilepsy age-related variables correlated strongly with each other among children with epilepsy onset ≤4 years (r = 0.53-0.66). The correlation between these variables was weaker with an onset ≥9 years (r =0.22-0.35). Correlation with QOL was clinically non-significant. These variables appear to measure the same phenomenon only in children with early epilepsy onset (<4 years) and explain little variance in QOL.

Push and Fluff technique for optimization of clot integration with stent-retriever: An in vitro model.

BACKGROUND: For stent-retriever (SR) thrombectomy, technical developments such as the Push and Fluff technique (PFT) appear to have a significant impact on procedural success. This study aimed to (1) quantify the enhancement in clot traction when using PFT as compared to the standard unsheathing technique (SUT) and (2) to evaluate the performance of PFT in new versus established users of the technique. METHODS: Operators were divided between established PFT and SUT users. Each experiment was labeled according to the SR size, utilized technique, and operator experience. A three-dimensional-printed chamber with a clot simulant was used. After each retriever deployment, the SR wire was connected to a force gauge. Tension was applied by pulling the gauge until clot disengagement. The maximal force was recorded. RESULTS: A total of 167 experiments were performed. The median overall force to disengage the clot was 1.11 pounds for PFT and 0.70 pounds for SUT (an overall 59.1% increment with PFT; p < 0.001). The PFT effect was consistent across different retriever sizes (69% enhancement with the 3 × 32mm device, 52% with the 4 × 28mm, 65% with the 4 × 41mm, 47% with the 6 × 37mm). The ratio of tension required for clot disengagement with PFT versus SUT was comparable between physicians who were PFT versus SUT operators (1.595 [0.844] vs. 1.448 [1.021]; p: 0.424). The PFT/SUT traction ratio remained consistent from passes 1 to 4 of each technique in SUT users. CONCLUSION: PFT led to reproduceable improvement in clot engagement with an average ∼60% increase in clot traction in this model and was found not to have a significant learning curve.

Cervical carotid occlusion in acute ischemic stroke: Should we give tPA?

Background: Acute ischemic stroke (AIS) due to cervical internal carotid artery (cICA) occlusion is challenging to treat, with the lower revascularization rates, higher risk for complications, and poor response to thrombolytic therapy compared to isolated intracranial occlusions. While emergent revascularization through mechanical thrombectomy (MT) improves outcomes, the impact of tissue plasminogen activator (tPA) on outcomes in this subgroup of patients remains unclear. The objective of this study is to report our preliminary experience in treating AIS with cICA occlusions secondary to severe atherosclerotic stenosis and to establish the need for further clinical studies to determine the optimal intervention strategy for these lesions. Methods: Data were collected on patients who presented with acute cICA occlusion who underwent MT and either acute or staged carotid angioplasty and stenting. We compare patients who received tPA to those who did not, analyzing revascularization times, outcomes, and complications between the two populations, and discuss how this influenced our preferred treatment approach. Results: Twenty-one patients met inclusion criteria, seven of who received tPA and 14 did not receive tPA before surgical intervention. Procedural and functional outcomes were similar between the two populations. TPA administration correlated with a higher rate of vessel reocclusion in staged procedures and trended toward higher rates of symptomatic ICH and 90-day mortality. Conclusion: Emergent revascularization with acute cICA stenting carries advantages, but its safety is precluded by tPA administration. We suggest a trial which randomizes patients with cICA occlusions to receiving either tPA or dual antiplatelet therapy before surgical intervention, aiming to ultimately improved outcomes in these patients.

Disease characteristics and psychosocial factors: explaining the expression of quality of life in childhood epilepsy.

OBJECTIVES: To explore, identify and understand the contribution that biomedical and psychosocial factors make to the assessment of health-related quality of life (HRQL) of children and youth with epilepsy using the CHEQOL-25. METHODS: We identified and measured variables that may influence HRQL; grouped the variables into four conceptual categories; and used simple and hierarchical linear regressions to model CHEQOL-25 as a function of these variable groupings. Participants were 8-15year olds with epilepsy and their parents. RESULTS: 131 child and parent pairs participated. Overall, the unique variances associated with the biomedical and psychosocial variables are R(2)=0.22 and 0.29, respectively, for child self-reported HRQL and R(2)=0.11 and 0.13, respectively, for parent-proxy report. CONCLUSIONS: This study increases our understanding of factors that contribute to the expression of HRQL in this population. These results should be interpreted with caution due to the limited sample size and large number of variables.

Magnetic resonance imaging features of the spinal cord in pediatric multiple sclerosis: a preliminary study.

INTRODUCTION: Spinal cord lesions in adults with multiple sclerosis (MS) are thought to contribute to disability. The magnetic resonance imaging (MRI) appearance and clinical correlates of spinal cord lesions in children with MS have not been reported. METHODS: T1-weighted pre- and post-gadolinium and T2-weighted TSE/FSE spine MR images of 36 children (age, 14.3 ± 3.3) with relapsing-remitting MS (annualized relapse rate, 0.7; disease duration, 7.5 ± 3.3 years) were analyzed for total lesion count, lesion location and length, intramedullary extent, and gadolinium enhancement. Clinical, demographic, laboratory, and MRI data were correlated. RESULTS: Lesions preferentially involved the cervical region, were predominantly focal, and involved only a portion of the transverse cord diameter. However, ten of 36 patients demonstrated longitudinally extensive lesions. Children with the highest clinical relapse rate also tended to have more spinal cord lesions and were more likely to accrue new lesions on serial spinal scans. CONCLUSION: These preliminary data suggest that MS lesions of the spinal cord in children are radiographically similar to that of adult-onset MS--supporting a common biology of pediatric- and adult-onset disease. However, children with relapsing-remitting MS can also develop longitudinally extensive lesions, suggesting that such lesions may be less specific for diseases such as neuromyelitis optica in pediatric patients. All patients recovered well from spinal cord attacks, and the presence of spinal cord lesions in the first few years of disease did not correlate with physical disability. Measures of spinal cord atrophy and longer periods of observation are required to determine the impact of spinal cord involvement in pediatric-onset MS.

Iatrogenic cortical pseudoaneurysm following ventriculoperitoneal shunt insertion presenting with intraventricular hemorrhage.

BACKGROUND: Cerebral pseudoaneurysm formation associated with ventricular catheterization is an exceedingly rare complication that results from direct catheter-induced injury to a vessel. We report a case of intracerebral pseudoaneurysm formation associated with ventricular catheterization in a patient with hydrocephalus following aneurysmal subarachnoid hemorrhage. CASE DESCRIPTION: The patient presented with aneurysmal subarachnoid hemorrhage and underwent partial endovascular embolization of the offending wide-necked basilar tip aneurysm with the plan for a Stage 2 stent-assisted coiling after initial recovery. Before discharge, a ventriculoperitoneal shunt (VPS) was placed for postaneurysmal hydrocephalus. Three weeks later, she presented with intraparenchymal and intraventricular hemorrhage. Angiography revealed a cortical aneurysm contiguous to the ventricular catheter of the VPS. She underwent microsurgical excision of the aneurysm, and a new VPS was placed after resolution of the intraventricular hemorrhage. She later underwent the second stage of the treatment and had an excellent neurological recovery to an independent state. CONCLUSION: Iatrogenic intracerebral pseudoaneurysm formation is an exceedingly rare complication of ventricular catheterization but is associated with significant mortality. Identifying a pseudoaneurysm in this context warrants prompt and definitive treatment with microsurgical or endovascular treatment.

Predictive measures and outcomes of extent of resection in juvenile pilocytic astrocytoma.

PURPOSE: The present study aims to determine the tumor-related, clinical, and demographic factors associated with extent of resection (EOR) and post-operative outcomes in JPA patients. METHODS: All patients with JPA, identified from a single-center brain tumour data base, were included in this retrospective analysis. Pre-operative MRI scans were reviewed by a single neurosurgeon blinded to the EOR. JPA cases that exhibited no residual tumor post-operatively were assigned to the GTR group, all other tumors were assigned to the

True Cortical Saccular Aneurysm Presenting as an Acute Subdural Hematoma.

BACKGROUND: Subdural hematoma, without any radiographic evidence of subarachnoid hemorrhage, is a rare presentation of a ruptured intracranial aneurysm. Even more rare is the occurrence of a pure subdural hematoma caused by a ruptured cortical saccular aneurysm. We report the eighth case of pure subdural hematoma secondary to a ruptured nonmycotic cortical berry aneurysm. CASE DESCRIPTION: We report a case of pure subdural hematoma secondary to a ruptured true saccular aneurysm of a cortical artery branch. The lesion was carefully delineated with computed tomography (CT) angiography (CTA) and cerebral angiography, and successfully treated with hematoma evacuation and clip ligation. The patient demonstrates no neurologic deficits 6 months after surgery, and CTA results remain negative. CONCLUSIONS: In the context of a presentation of spontaneous subdural hematoma, intracerebral aneurysm rupture should be considered as a possible etiology. Prompt vascular imaging with careful evaluation of the entire cerebral vasculature, including the cortical vessels, should be considered.

MRI and laboratory features and the performance of international criteria in the diagnosis of multiple sclerosis in children and adolescents: a prospective cohort study.

BACKGROUND: MRI and laboratory features have been incorporated into international diagnostic criteria for multiple sclerosis. We assessed the pattern of MRI lesions and contributions of cerebrospinal fluid (CSF) and serum antibody findings that best identifies children with multiple sclerosis, and the applicability of international diagnostic criteria in the paediatric context. METHODS: In this prospective cohort study, detailed clinical assessments, serum and CSF studies, and MRI scans were done in youth (aged 0·46-17·87 years) with incidental acquired demyelinating syndrome. Participants were examined prospectively to identify relapsing disease. All MRI scans were assessed using a validated scoring method. A random forest classifier identified imaging and laboratory features that best predicted a multiple sclerosis or monophasic outcome. Performance of the 2001, 2010, and 2017 international McDonald criteria for the diagnosis of multiple sclerosis, the 2016 MRI in multiple sclerosis (MAGNIMS) criteria, and our 2011 proposed (Verhey) criteria were determined; performance was adjudicated with generalised linear models. FINDINGS: Between Sept 1, 2004, and June 30, 2017, we included 324 participants with median follow-up of 72 months (range 6-150), 71 (22%) participants with multiple sclerosis, 237 (73%) with monophasic acquired demyelinating syndrome, 14 (4%) with relapsing non-multiple sclerosis, and two (1%) with alternative diagnoses. We scored 2391 brain, 444 spinal, and 67 dedicated orbital MRI scans. One or more T1 hypointense lesions plus one or more periventricular lesions (Verhey criteria) best predicted multiple sclerosis outcome. Performance of the 2017 McDonald criteria was comparable to the 2010 McDonald criteria and was easier to adjudicate. The ability of CSF oligoclonal bands to substitute for the requirement for both enhancing and non-enhancing lesions in the 2017 McDonald criteria improved its performance compared with the 2010 criteria. Myelin oligodendrocyte testing at baseline did not improve performance of the 2017 McDonald criteria. INTERPRETATION: The 2017 McDonald criteria for the diagnosis of multiple sclerosis, as applied at the time of incident attack, perform well in identifying children and youth with multiple sclerosis, indicating that the same diagnostic criteria for multiple sclerosis apply across the age span. The presence of so-called black holes on MRI and periventricular lesions at baseline (Verhey criteria) also effectively distinguish children with multiple sclerosis from children with monophasic demyelination. The presence of CSF oligoclonal bands improve diagnostic accuracy. Myelin oligodendrocyte glycoprotein antibodies identify children with acute disseminated encephalomyelitis, and those with relapsing non-multiple sclerosis, most of whom do not meet 2017 McDonald criteria at onset. FUNDING: The Multiple Sclerosis Scientific Research Foundation and The Children's Hospital of Philadelphia.

Monophasic demyelination reduces brain growth in children.

OBJECTIVE: To investigate how monophasic acquired demyelinating syndromes (ADS) affect age-expected brain growth over time. METHODS: We analyzed 83 pediatric patients imaged serially from initial demyelinating attack: 18 with acute disseminated encephalomyelitis (ADEM) and 65 with other monophasic ADS presentations (monoADS). We further subdivided the monoADS group by the presence (n = 33; monoADSlesion) or absence (n = 32; monoADSnolesion) of T2 lesions involving the brain at onset. We used normative data to compare brain volumes and calculate age- and sex-specific z scores, and used mixed-effect models to investigate their relationship with time from demyelinating illness. RESULTS: Children with monophasic demyelination (ADEM, non-ADEM with brain lesions, and those without brain involvement) demonstrated reduced age-expected brain growth on serial images, driven by reduced age-expected white matter growth. Cortical gray matter volumes were not reduced at onset but demonstrated reduced age-expected growth afterwards in all groups. Brain volumes differed from age- and sex-expected values to the greatest extent in children with ADEM. All patient groups failed to recover age-expected brain growth trajectories. CONCLUSIONS: Brain volume, and more importantly age-expected brain growth, is negatively affected by acquired demyelination, even in the absence of chronicity, implicating factors other than active inflammation as operative in this process.

Clinical and magnetic resonance imaging (MRI) distinctions between tumefactive demyelination and brain tumors in children.

Tumefactive demyelinating lesions can be difficult to distinguish from tumors. Clinical and magnetic resonance imaging features of children with tumefactive demyelination and supratentorial brain tumors were compared. Patients were identified through a 23-site national demyelinating disease study, and from a single-site neuroradiology database. For inclusion, lesions met at least 1 of 3 criteria: maximal cross-sectional diameter >20 mm, local or global cerebral mass effect, or presence of perilesional edema. Thirty-one children with tumefactive demyelination (5 with solitary lesions) were identified: 27 of 189 (14.3%) from the demyelinating disease study and 4 from the database. Thirty-three children with tumors were identified. Children with tumefactive demyelination were more likely to have an abnormal neurologic examination and polyfocal neurologic deficits compared to children with tumors. Tumefactive demyelination was distinguished from tumor by the presence of multiple lesions, absence of cortical involvement, and decrease in lesion size or detection of new lesions on serial imaging.

Outcome measures in relapsing-remitting multiple sclerosis: capturing disability and disease progression in clinical trials.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease that manifests as acute relapses and progressive disability. As a primary endpoint for clinical trials in MS, disability is difficult to both characterize and measure. Furthermore, the recovery from relapses and the rate of disability vary considerably among patients. Given these challenges, investigators have developed and studied the performance of various outcome measures and surrogate endpoints in MS clinical trials. This review defines the outcome measures and surrogate endpoints used to date in MS clinical trials and presents challenges in the design of both adult and pediatric trials.

Outcomes trajectories in children with epilepsy: hypotheses and methodology of a Canadian longitudinal observational study.

BACKGROUND: The impact of childhood epilepsy can only be appreciated by understanding that epilepsy comprises a set of complex neurobehavioral conditions with significant social consequences, and not simply disorders of recurrent seizures. Our objective is to describe the hypotheses and methodology behind a large prospective longitudinal study that is based on a conceptual framework for understanding health outcomes. The study will quantify the specific influences--direct, mediating or moderating--that various epilepsy, comorbid, child, and family variables exert on health over the early life course. METHODS: The target population is 8- to 14-year-old children with epilepsy and their caregivers from across Canada. Children, caregivers, and health professionals are completing 17 measures at five visits over a 28-month period. We have selected measures based on content, the source of the items, psychometric properties, and provisions for child self-report. Our cross-sectional and longitudinal design includes a relational model for structural equation modeling of specific biomedical and psychosocial variables with hierarchical direction of influence. To measure change over time, we will use hierarchical linear modeling. SIGNIFICANCE: This article reports the framework for interpreting future data. We believe that it will help researchers consider their methodology and encourage them to plan and execute longitudinal studies. Furthermore, the article will help clinical readers identify what to look for when evaluating outcomes research. It is our belief that the next generation of research to understand life-course effect in the lives of children and youth with chronic conditions and their families must occur over real time.

Standardized magnetic resonance imaging acquisition and reporting in pediatric multiple sclerosis.

Magnetic resonance (MR) imaging is one of the most important paraclinical tools for the diagnosis of multiple sclerosis (MS), and monitoring of disease progression and treatment response. This article provides clinicians and neuroradiologists caring for children with demyelinating disorders with a suggested standard MR imaging acquisition and reporting protocol, and defines a standard lexicon for lesion features typical of MS in children. As there is considerable overlap between the MR imaging features of pediatric- and adult-onset MS, the recommendations provided herein may be of relevance to radiologists and clinicians caring for adults with multiple sclerosis.