Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Neurology
Total Results:
23449
European journal of physical & rehabilitation medicine. 2019:55(2):250-257.DOI: 10.23736/S1973-9087.18.05326-1
Use of 3D gait analysis as predictor of Achilles tendon lengthening surgery outcomes in children with cerebral palsy
BACKGROUND:In children with spastic cerebral palsy (CP), the treatment of equinus foot with Achilles tendon lengthening (ATL) surgery is associated with high incidence of overcorrection, which may result in crouch gait. AIM/OBJECTIVE:We aimed to assess if gait pattern in preoperative time could be a predictor of the surgery outcome. DESIGN/METHODS:Cross-sectional retrospective study. SETTING/METHODS:Movement Analysis Lab of IRCCS San Raffaele Pisana Hospital in Rome (Italy). POPULATION/METHODS:Eighteen children (mean age 9.6±4.7 years) with spastic diplegia CP who underwent bilateral ATL surgery to correct equinus foot were involved. METHODS:Participants underwent 3D gait analysis before and approximately 12 months after surgery. Primary measures were spatiotemporal, kinematic (summarized by Gait Variable Scores, GVSs) and kinetic parameters. The gait patterns for each leg was defined from kinematic data, using a quantitative classification: plantar flexor knee extension (PFKE) index. The CP group was split into true equinus and jump gait. RESULTS:The equinus foot was successfully corrected as demonstrated by the improvement of GVS ankle dorsi-plantarflexion. However, there was a high rate of overcorrection in the true equinus, characterized by increases in knee flexion-extension GVS (8.7° pre vs. 16.7° post P<0.05) and knee flexion angle at initial contact (5.2° vs. 20.6° P<0.05) and by a decrease in the maximum ankle power generated at push-off (1.49 vs. 0.83 W/kg P<0.05). CONCLUSIONS:Assessment of motor phenotype in preoperative time are good predictors of the results of ATL surgery. In children with true equinus gait, the increase of knee flexion subsequent to ATL is an early indicator that this technique will lead to crouch gait. These results show the influence of true equinus and jump gait patterns on the outcomes of the ATL. CLINICAL REHABILITATION IMPACT/CONCLUSIONS:Therefore, we propose that this approach could have clinical value to evaluate and prescribe rehabilitation in children with CP disease, proposing different solutions depending on motor phenotype.
PMID: 30156089
ISSN: 1973-9095
CID: 5353262
Special issue in honour of the first editor of EJN, Ray Guillery [Editorial]
PMID: 30953594
ISSN: 1460-9568
CID: 4095312
Evaluating the efficacy and safety of 6-week extended interval dosing of natalizumab via a prospective, controlled, randomized phase 3B study [Meeting Abstract]
Background: Natalizumab, a highly efficacious therapy for relapsing-remitting multiple sclerosis (RRMS), is also associated with progressive multifocal leukoencephalopathy (PML) risk. A recent analysis of the TOUCH dataset demonstrated that extended interval dosing (EID) is associated with significantly lower PML risk in anti-JC virus antibody positive patients. There have been no randomized studies to assess EID efficacy.
Objective(s): To describe the design of a phase 3b study to evaluate the efficacy of EID natalizumab initiated after a stable period of standard interval dosing (SID) compared with continuing SID.
Method(s): A prospective, interventional, controlled, randomized, open-label, rater-blinded, global study will be conducted. Eligibility requirements include age 18-60, Expanded Disability Status Scale <=5.5, RRMS, stable on SID natalizumab for >=1 year with no relapses in the prior year, no prior immunosuppressant use, and no gadolinium-enhancing (Gd+) lesions at screening. Patients will be randomized 1:1 to natalizumab SID (every 4 weeks) or EID (every 6 weeks). Study duration will be 88 weeks (4-week screening, 72 weeks randomized treatment, 12 weeks follow-up). The primary endpoint is number of new/newly enlarging T2 lesions at 48 weeks. Key secondary endpoints include time to relapse, relapse rate, number of new radiologic lesions, and incidence of serious adverse events. Exploratory endpoints include Timed 25-Foot Walk, Nine-Hole Peg Test, Symbol Digit Modality Test, and confirmed disability worsening or improvement. Data on natalizumab serum concentration, alpha-4 integrin saturation, lymphocyte counts, and body weight will be collected to explore relationships between pharmacokinetics/pharmacodynamics and efficacy.
Result(s): Approximately 480 patients will be enrolled. The rationale for study sample size, inclusion criteria, dosing intervals, and endpoints will be presented.
Conclusion(s): This study will provide the first randomized, controlled efficacy data for patients treated with EID natalizumab and will inform on the potential of EID as a future PML risk mitigation strategy
Objective(s): To describe the design of a phase 3b study to evaluate the efficacy of EID natalizumab initiated after a stable period of standard interval dosing (SID) compared with continuing SID.
Method(s): A prospective, interventional, controlled, randomized, open-label, rater-blinded, global study will be conducted. Eligibility requirements include age 18-60, Expanded Disability Status Scale <=5.5, RRMS, stable on SID natalizumab for >=1 year with no relapses in the prior year, no prior immunosuppressant use, and no gadolinium-enhancing (Gd+) lesions at screening. Patients will be randomized 1:1 to natalizumab SID (every 4 weeks) or EID (every 6 weeks). Study duration will be 88 weeks (4-week screening, 72 weeks randomized treatment, 12 weeks follow-up). The primary endpoint is number of new/newly enlarging T2 lesions at 48 weeks. Key secondary endpoints include time to relapse, relapse rate, number of new radiologic lesions, and incidence of serious adverse events. Exploratory endpoints include Timed 25-Foot Walk, Nine-Hole Peg Test, Symbol Digit Modality Test, and confirmed disability worsening or improvement. Data on natalizumab serum concentration, alpha-4 integrin saturation, lymphocyte counts, and body weight will be collected to explore relationships between pharmacokinetics/pharmacodynamics and efficacy.
Result(s): Approximately 480 patients will be enrolled. The rationale for study sample size, inclusion criteria, dosing intervals, and endpoints will be presented.
Conclusion(s): This study will provide the first randomized, controlled efficacy data for patients treated with EID natalizumab and will inform on the potential of EID as a future PML risk mitigation strategy
EMBASE:628003471
ISSN: 1477-0970
CID: 3931522
Effects of high myopia on retinal layer rates of change as measured by optical coherence tomography [Meeting Abstract]
Background: Myopia's axial elongation of the eye causes an irregularly shaped retina. Cross-sectional studies show that increasing diopters and axial lengths in myopia correlate negatively with Optical Coherence Tomography (OCT) derived measures of Retinal Nerve Fiber Layer (RNFL) thickness. This has largely precluded including OCT data from high myopia individuals in Multiple Sclerosis (MS) and other studies. OCT is a promising marker of neurodegeneration in MS. However, the impact of high myopia in longitudinal studies remains to be investigated.
Objective(s): To assess the impact of high myopia on rates of change in OCT retinal layer thicknesses in MS patients and healthy controls (HC).
Method(s): A 1:2 age and sex matching scheme was used in the MS [13 high myopia (MSHM): 26 non myopia (MSNM)] and HC [7 high myopia (HCHM): 14 non myopia (HCNM)] cohorts. OCT thickness measures of the peripapillary RNFL (pRNFL), ganglion cell+inner plexiform layer (GCIP), and other retinal layers were determined using a validated segmentation algorithm. Mixed effects linear regression was used in statistical analyses.
Result(s): Baseline MSHM eyes had lower GCIP (-4.01 mum, p = 0.06) and pRNFL thicknesses (-8.15 mum, p = 0.04), as compared to MSNM eyes. HC GCIP and pRNFL thicknesses were lower in HCHM than HCNM eyes (-4.15 mum, p = 0.01 and -0.84 mum, p = 0.83 respectively). Despite cross-sectional differences in retinal layer thicknesses in eyes stratified by myopia, longitudinal (median duration of follow-up= 4.6, 6.9, 4.0, 5.1 years in MSHM, MSNM, HCHM, and HCNM respectively) rates of retinal layer change did not differ between participants with and without high myopia. In the MS cohort, rates of thinning were significant in both groups but there was no difference between rates of GCIP and pRNFL thinning among MSHM and MSNM (DELTA0.07 mum/y, p = 0.71 and DELTA0.12 mum/y, p = 0.52 respectively) eyes. Similarly, no difference in rates of GCIP and pRNFL change was found between HCHM and HCNM (DELTA0.06 mum/y, p = 0.49 and DELTA0.21 mum/y, p = 0.22 respectively) eyes. Similar results were observed for the inner and outer nuclear layers in MS and HCs.
Conclusion(s): Although cross-sectional retinal thickness measures may vary due to myopia, longitudinal rates of retinal change appear unaffected. Therefore, despite longstanding opinion, our findings suggest high myopia may not confound longitudinal OCT analyses. Future research is needed to verify and validate our preliminary findings in larger, longitudinal studies
Objective(s): To assess the impact of high myopia on rates of change in OCT retinal layer thicknesses in MS patients and healthy controls (HC).
Method(s): A 1:2 age and sex matching scheme was used in the MS [13 high myopia (MSHM): 26 non myopia (MSNM)] and HC [7 high myopia (HCHM): 14 non myopia (HCNM)] cohorts. OCT thickness measures of the peripapillary RNFL (pRNFL), ganglion cell+inner plexiform layer (GCIP), and other retinal layers were determined using a validated segmentation algorithm. Mixed effects linear regression was used in statistical analyses.
Result(s): Baseline MSHM eyes had lower GCIP (-4.01 mum, p = 0.06) and pRNFL thicknesses (-8.15 mum, p = 0.04), as compared to MSNM eyes. HC GCIP and pRNFL thicknesses were lower in HCHM than HCNM eyes (-4.15 mum, p = 0.01 and -0.84 mum, p = 0.83 respectively). Despite cross-sectional differences in retinal layer thicknesses in eyes stratified by myopia, longitudinal (median duration of follow-up= 4.6, 6.9, 4.0, 5.1 years in MSHM, MSNM, HCHM, and HCNM respectively) rates of retinal layer change did not differ between participants with and without high myopia. In the MS cohort, rates of thinning were significant in both groups but there was no difference between rates of GCIP and pRNFL thinning among MSHM and MSNM (DELTA0.07 mum/y, p = 0.71 and DELTA0.12 mum/y, p = 0.52 respectively) eyes. Similarly, no difference in rates of GCIP and pRNFL change was found between HCHM and HCNM (DELTA0.06 mum/y, p = 0.49 and DELTA0.21 mum/y, p = 0.22 respectively) eyes. Similar results were observed for the inner and outer nuclear layers in MS and HCs.
Conclusion(s): Although cross-sectional retinal thickness measures may vary due to myopia, longitudinal rates of retinal change appear unaffected. Therefore, despite longstanding opinion, our findings suggest high myopia may not confound longitudinal OCT analyses. Future research is needed to verify and validate our preliminary findings in larger, longitudinal studies
EMBASE:628003357
ISSN: 1477-0970
CID: 3931532
Progressive multiple sclerosis is associated with accelerated inner and outer retinal layer atrophy [Meeting Abstract]
Background: Optical coherence tomography (OCT) studies have shown that retinal nerve fiber layer (RNFL) and ganglion cell + inner plexiform layer (GCIP) thinning are accelerated in multiple sclerosis (MS). Increased inner nuclear layer (INL) thickness has been associated with inflammatory disease activity, but decreased thicknesses of the INL and outer nuclear layer (ONL) have also been identified in a subset of patients with more severe disability. INL atrophy has also been found post-mortem in MS eyes, more frequently in progressive MS (PMS). These data suggest that there exist differences in retinal pathology at various stages of the disease, however these have been incompletely characterized, as the vast majority of OCT studies comparing retinal measures between MS subtypes have been cross-sectional, with small numbers of PMS eyes.
Objective(s): To assess the effects of age and MS subtype on longitudinal changes in retinal layer thicknesses.
Method(s): A cohort of MS patients and healthy controls (HC), followed with serial spectral-domain OCT, was evaluated. Retinal layer thicknesses were derived utilizing a validated, automated segmentation algorithm. Statistical analyses were performed with mixed-effects linear regression models.
Result(s): Data from 364 MS (178 relapsing-remitting MS [RRMS], 186 PMS) and 66 HC participants were analyzed. Median follow-up duration was 3.6 years. Higher age was associated with slower rates of RNFL atrophy in MS (p<0.001), but not in HC. Rates of GCIP atrophy did not differ across age in MS, but in HC higher age was associated with accelerated rates of GCIP atrophy (p=0.006). The proportion of RNFL and GCIP atrophy in MS attributable to normal aging increased from 42.7% and 16.7% respectively at age 25 years, to 83.7% and 81.1% at age 65 years. PMS was independently associated with accelerated RNFL and GCIP atrophy compared to RRMS (RNFL: p=0.002; GCIP: p=0.001). Higher age was associated with accelerated INL and ONL atrophy and this relationship was similar in MS and HC. INL and ONL atrophy rates were faster in PMS compared to HC (INL: p=0.03; ONL: p=0.04) and RRMS (INL: p=0.008; ONL: p=0.01), but did not differ between RRMS and HC.
Conclusion(s): PMS is independently associated with accelerated retinal layer atrophy, and INL and ONL atrophy may be novel biomarkers of neurodegeneration in PMS. The effects of normal aging on retinal layer thicknesses should be considered when designing clinical trials incorporating OCT measures as outcomes
Objective(s): To assess the effects of age and MS subtype on longitudinal changes in retinal layer thicknesses.
Method(s): A cohort of MS patients and healthy controls (HC), followed with serial spectral-domain OCT, was evaluated. Retinal layer thicknesses were derived utilizing a validated, automated segmentation algorithm. Statistical analyses were performed with mixed-effects linear regression models.
Result(s): Data from 364 MS (178 relapsing-remitting MS [RRMS], 186 PMS) and 66 HC participants were analyzed. Median follow-up duration was 3.6 years. Higher age was associated with slower rates of RNFL atrophy in MS (p<0.001), but not in HC. Rates of GCIP atrophy did not differ across age in MS, but in HC higher age was associated with accelerated rates of GCIP atrophy (p=0.006). The proportion of RNFL and GCIP atrophy in MS attributable to normal aging increased from 42.7% and 16.7% respectively at age 25 years, to 83.7% and 81.1% at age 65 years. PMS was independently associated with accelerated RNFL and GCIP atrophy compared to RRMS (RNFL: p=0.002; GCIP: p=0.001). Higher age was associated with accelerated INL and ONL atrophy and this relationship was similar in MS and HC. INL and ONL atrophy rates were faster in PMS compared to HC (INL: p=0.03; ONL: p=0.04) and RRMS (INL: p=0.008; ONL: p=0.01), but did not differ between RRMS and HC.
Conclusion(s): PMS is independently associated with accelerated retinal layer atrophy, and INL and ONL atrophy may be novel biomarkers of neurodegeneration in PMS. The effects of normal aging on retinal layer thicknesses should be considered when designing clinical trials incorporating OCT measures as outcomes
EMBASE:628003737
ISSN: 1477-0970
CID: 3931542
Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids
The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.
PMCID:6467258
PMID: 30926973
ISSN: 1546-1718
CID: 4094682
Linking spherical mean diffusion weighted signal with intra-axonal volume fraction
Diffusion MRI has been widely used to assess brain tissue microstructure. However, the conventional diffusion tensor imaging (DTI) is inadequate for characterizing fiber direction or fiber density in voxels with crossing fibers in brain white matter. The constrained spherical deconvolution (CSD) technique has been proposed to measure the complex fiber orientation distribution (FOD) using a single high b-value (b ≥ 3000 s/mm2) to derive the intra-axonal volume fraction (Vin) from the calculated FOD. Recently, the spherical mean technique (SMT) was developed to fit Vin directly from a multi-compartment model with multi-shell b-values. Although different numbers of b-values are needed in the two techniques, both methods have been suggested to be related to the spherical mean diffusion weighted signal (S¯). The current study compared the two techniques on the same high-quality Human Connectome Project diffusion data and investigated the relation between S¯ and Vin systematically. At high b-values (b ≥ 3000 s/mm2), S¯ is linearly related to Vin, and S¯ provides similar contrast with Vin in white matter. At low b-values (b ~ 1000 s/mm2), the linear relation between S¯ and Vin is sensitive to the variations of intrinsic diffusivity. These results demonstrate that S¯ measured with the typical b-value of 1000 s/mm2 is not an indicator of Vin, and previous DTI studies acquired with b = 1000 s/mm2 cannot be re-analyzed to provide Vin-weighted contrast.
PMCID:6331230
PMID: 30439515
ISSN: 1873-5894
CID: 3642282
Effet du traitement par fingolimod chez des enfants ayant une sclerose en plaques (SEP): Resultats complementaires de l'etude PARADIGMS [Meeting Abstract]
Introduction: Dans PARADIGMS, premiere etude phase III en double aveugle dans la SEP pediatrique, le fingolimod a diminue significativement le taux annualise de poussees (TAP) de 82 % versus l'interferon (IFN) beta-1a. Objectifs: Effectuer des analyses dans des sous-groupes (anticorps neutralisants anti-IFN, naifs de traitement); evaluer l'effet chez les patients plus jeunes et prepuberes, la progression du handicap, la qualite de vie. Patients et Methodes: Les analyses de sous-groupes des criteres principal (TAP) et secondaire principal (nouvelles lesions T2, NT2) et post-hoc sur la progression confirmee du handicap ont ete realisees. La qualite de vie (QdV) liee a la sante a ete evaluee par les patients ou les parents a l'aide du questionnaire PedsQL (Quality of Life) avant et a la fin de l'etude (jusqu'a 2 ans): changements du score total et des scores sante physique et sante psychosociale. Resultats: Dans toutes les analyses de sous-groupes, le fingolimod a diminue significativement le TAP (81,5-85,8 %) et NT2 (47,6-53,4 %) versus l'IFNbeta-1a. Le risque de progression du handicap confirmee a 3 mois etait reduit de 77,2 % ([HR] = 0,23, p = 0,007). L'analyse post-hoc a confirme son effet positif sur les scores totaux et de sante physique de QdV rapportes par les patients et les parents, et de sante psychosociale rapporte par les patients versus l'IFN beta-1a (tous p < 0,05). Discussion(s): Le fingolimod dans la SEP pediatrique a ete associe a un controle de l'activite de la maladie dans toutes les analyses complementaires, chez les patients traites precedemment ou non, et ce de maniere plus marquee chez les patients plus jeunes. Des benefices sur la progression du handicap ont ete observes sur une duree de traitement allant jusqu'a 2 ans. Conclusion(s): Le fingolimod versus IFN beta-1a a ete associe a une amelioration significative du controle de l'activite de la maladie et de la qualite de vie liee a la sante.
EMBASE:2001636410
ISSN: 0035-3787
CID: 3789912
Familial history of autoimmune disorders among pediatric multiple sclerosis patients [Meeting Abstract]
Background: Adult MS research has identified an increased prevalence of various autoimmune conditions among family members of diagnosed patients. There has not been comparable studies of pediatric MS populations, while this cohort may represent a unique population from a risk factors perspective.
Objective(s): This study was undertaken to quantify the incidence of autoimmune conditions among first and second degree relatives of pediatric MS patients as compared to controls. The study sought to quantify both the rate, type and patterns of diagnoses seen throughout family members of pediatric MS patients.
Method(s): A multi center case-control study of risk factors for pediatric MS has been ongoing for since 2011. Pediatric patients with a diagnosis of MS and pediatric controls were recruited to provide data and biologic specimens for a number of research projects. Included in this effort was the acquisition of family history questionnaires. The medical data from these questionnaires were analyzed for the presence of certain medical diagnoses among first and second degree relatives. Logistic regression models were used to test for differences between cases and controls in reporting a family history of autoimmune diseases, when adjusting for sex, race, age, ethnicity, and mother's education level. Odds ratios and 95% confidence intervals were calculated based on the logistic regression models.
Result(s): Several conditions were found to have statistically significant differences in prevalence among first and second degree family members of MS patients as compared to controls. Diabetes, thyroid disorders and rheumatoid arthritis has the most notable differences between patients and controls while eczema and psoriasis were not different. The odds ratio of any family history of autoimmune disease was 2.27 among cases compared to controls. The odds ratio of an autoimmune disease among family members was significantly higher among paternal relatives as compared to maternal relatives (eg OR of 6.37 compared to 2.64).
Conclusion(s): This study has identified an increased prevalence of certain autoimmune disorders among first and second degree family members of pediatric MS patients. This aligns with prior findings among adult populations that found higher rates of autoimmune disorders among family members of adult onset MS patients. Novel to this study was the difference in relative risk of autoimmune conditions occurring in paternal versus maternal family members
Objective(s): This study was undertaken to quantify the incidence of autoimmune conditions among first and second degree relatives of pediatric MS patients as compared to controls. The study sought to quantify both the rate, type and patterns of diagnoses seen throughout family members of pediatric MS patients.
Method(s): A multi center case-control study of risk factors for pediatric MS has been ongoing for since 2011. Pediatric patients with a diagnosis of MS and pediatric controls were recruited to provide data and biologic specimens for a number of research projects. Included in this effort was the acquisition of family history questionnaires. The medical data from these questionnaires were analyzed for the presence of certain medical diagnoses among first and second degree relatives. Logistic regression models were used to test for differences between cases and controls in reporting a family history of autoimmune diseases, when adjusting for sex, race, age, ethnicity, and mother's education level. Odds ratios and 95% confidence intervals were calculated based on the logistic regression models.
Result(s): Several conditions were found to have statistically significant differences in prevalence among first and second degree family members of MS patients as compared to controls. Diabetes, thyroid disorders and rheumatoid arthritis has the most notable differences between patients and controls while eczema and psoriasis were not different. The odds ratio of any family history of autoimmune disease was 2.27 among cases compared to controls. The odds ratio of an autoimmune disease among family members was significantly higher among paternal relatives as compared to maternal relatives (eg OR of 6.37 compared to 2.64).
Conclusion(s): This study has identified an increased prevalence of certain autoimmune disorders among first and second degree family members of pediatric MS patients. This aligns with prior findings among adult populations that found higher rates of autoimmune disorders among family members of adult onset MS patients. Novel to this study was the difference in relative risk of autoimmune conditions occurring in paternal versus maternal family members
EMBASE:628004290
ISSN: 1477-0970
CID: 3931562
Natalizumab extended interval dosing (EID) is associated with a significant reduction in progressive multifocal leukoencephalopathy (PML) risk compared with standard interval dosing (SID) in the TOUCH Prescribing Program [Meeting Abstract]
Introduction: Natalizumab, approved for 300 mg intravenous every-4-weeks dosing, is associated with PML risk. Objective(s): To determine whether natalizumab EID is associated with reduced PML risk compared with SID. Patients and Methods: Average dosing intervals (ADIs) were >= 3 to < 5 weeks for SID and > 5 to <= 12 weeks for EID. The primary analysis assessed ADI in the last 18 months of infusion history. The secondary analysis identified any prolonged period of EID at any time in the infusion history. The tertiary analysis assessed ADI over the full infusion history. Result(s): In primary analyses, median exposure (months) was 44 for SID and 59 for EID. The PML HR (95% confidence interval) was 0.06 (0.01-0.22; P < 0.001) for primary and 0.12 (0.05-0.29; P < 0.001) for secondary analyses; no EID PML cases were observed in tertiary analyses (Kaplan-Meier log-rank test P = 0.02). Discussion(s): NA. Conclusion(s): In JCV Ab + patients, natalizumab EID is associated with a clinically and statistically significant reduction in PML risk as compared with SID.
EMBASE:2001636370
ISSN: 0035-3787
CID: 3789922
