Impaired Ambulation Research Articles

Quality of life analysis of patients treated with cetuximab or cisplatin for locoregionally advanced squamous cell carcinoma of head and neck in the United States

BackgroundTo compare quality of life of patients treated with cetuximab with or without radiation therapy (±RT) vs. cisplatin±RT for locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) in the real-world setting.MethodsIn this retrospective observational study, electronic medical records and Patient Care Monitor (PCM) survey data from the Vector Oncology Data Warehouse were utilized from adult patients in the United States who received initial treatment with cetuximab±RT or cisplatin±RT for locoregionally advanced SCCHN between January 1, 2007 and January 1, 2017. Quality of life was assessed using PCM index scores and individual PCM items. Cetuximab±RT and cisplatin±RT cohorts were balanced using propensity score weighting. Linear mixed models were used to assess the impact of baseline demographic and clinical characteristics on PCM endpoints.ResultsOf 531 patients with locoregionally advanced SCCHN, 187 received cetuximab±RT, and 344 received cisplatin±RT. Before propensity score weighting, the cetuximab±RT cohort was older (mean [SD] age of 63.9 [9.6] years vs. 57.4 [8.6] years), and more likely to be white (82.4% vs. 72.4%) compared to the cisplatin±RT cohort. After propensity score weighting, the two cohort subsamples (cetuximab±RT, N = 60; cisplatin±RT, N = 177) with PCM data showed no significant differences in General Physical Symptoms, Treatment Side Effects, Impaired Ambulation, or Impaired Performance index scores. Patients in the cetuximab±RT cohort had higher Acute Distress index (p = 0.023), Despair index (p = 0.011), and rash (p = 0.003) scores but lower numbness/tingling scores (p = 0.022) than patients in the cisplatin±RT cohort.ConclusionsSignificant group differences were observed in this comparative analysis, as the cetuximab±RT cohort had significantly higher Acute Distress index, Despair index, and rash scores compared with the cisplatin±RT cohort but lower numbness/tingling scores. These patterns of symptoms appear consistent with previously reported symptoms associated with the treatment of SCCHN.

STIFF PERSON SYNDROME (SPS) THE IMPORTANCE OF EXTENSIVE PHYSICAL EXAMINATION

Stiff Person Syndrome (SPS) is a rare condition with a prevalence of one to two cases per million and an incidence of one case per year. Characterized by progressive muscle stiffening, rigidity and spasm, mainly involve the axial muscles, resulting in severely impaired ambulation. The pathogenesis is not that clear. Classic SPS presents with extreme and persistent rigidity and stiffness of truncal and proximal limb muscles, significant lumber/cervical lordosis resulting from simultaneous actions of opposing paraspinous muscles are the hallmark. Wide and unsteady gait (Frankenstein’s gait) resulting from stiff muscles increases the risk of fall and fracture. Patient’s ADLs get severely restricted progressively. Startle reflex which is a superimposed episodic muscle spasm precipitated by sudden movement, noise, or emotional upset is a sensitive and specific feature of SPS and can be visible and palpable. Autonomic dysfunctions are common and are common cause of death in patients with SPS. In cases of partial SPS, we can find that truncal muscles are spared and limb muscles are affected, hence the term stiff-limb syndrome is used sometimes. Can involve a limb or focal part of a limb. As for treatment, symptom control and improving mobility and overall functionality is the primary target. High dose benzodiazepine is the best initial treatment. Those who are refractory can be benefit from Baclofen, IVIG, Plasma exchange, biological agent, e.g. Rituximab. Treatment of primary malignancies in paraneoplastic SPS can achieve remission. Keywords: Stiff Person Syndrome, clinical features, diagnosis and treatment.

SAT-LB68 A Rare De Novo Mutation in LRP5 Gene in an Adolescent Female With Juvenile Onset Primary Osteoporosis

Background: Juvenile onset of primary osteoporosis is a rare skeletal disorder with a highly heterogenous clinical presentation and complex poorly understood genetic etiology. Low-density lipoprotein receptor-related protein 5 (LRP5), a Wnt-β-catenin pathway receptor involved in bone mineral density (BMD) regulation, has been reported in children with primary osteoporosis mainly due to missense and frame-shift mutations. To our knowledge, there is only one report of in-frame deletions in exon 21 possibly being implicated in pregnancy related osteoporosis (1). We report the first case of a rare heterozygous de novo in-frame deletion in exon 21 of LRP5 gene in a girl with juvenile onset primary osteoporosis. Clinical Case: A 7.5 yo previously healthy European-African-American female born to non-consanguineous family, was noted to have left ankle and bilateral wrists fractures during sport activities occurring over the span of 1 y. On exam, she was of normal stature, had normal sclerae and vision, but was found to have hypermobile joints. Initial blood work revealed an elevated iPTH 72 pg/mL (9-59), normal Ca 9.6 mg/dL (8.9-10.4), and low 25OH-Vitamin D 17 ng/mL (30-100), which normalized with supplementation to 30.4 ng/mL. By 10.5 yo, she had sustained multiple sports related and pathologic fractures of long bones with progressive bone pain and functional ambulatory impairment. Radiographic evaluation showed osteopenia, multiple healed long bone fractures with presumed non-ossifying fibroma in the distal right femoral metaphysis, and subtle height loss of T4-5 vertebrae. CT bone densitometry at 12 yo showed low mean cancellous lumbar vertebral BMD of 190 mg/cm3 (ref. 285 ± 45) and normal cortical BMD of the femoral midshaft of 1977 mg/cm3 (ref. 2000 ± 60). Genetic testing for Osteogenesis Imperfecta returned negative for COL1A1 and COL1A2 mutations. Whole exome sequencing (WES) revealed a rare, de novo heterozygous mutation in exon 21 that involved deletion of nucleotides 4454 to 4465 resulting in an in-frame deletion of amino acid 1485 to 1488. This mutation is predicted to be deleterious by in silico analysis. Conclusion: We present the first case of a young female with progressive pathologic fractures, functional ambulatory impairment, and low BMD in childhood, consistent with juvenile onset primary osteoporosis. WES revealed a rare de novo heterozygous in-frame deletion mutation in LRP5, providing a plausible biological mechanism for her clinical presentation, and further contributing to the increasing genetic heterogeneity of juvenile onset primary osteoporosis and LRP5-related bone disorders. Reference: (1) Cook, F., Mumm, S., Whyte, M., Wenkert, D. Pregnancy-associated osteoporosis with a heterozygous deactivating LDL receptor-related protein 5 (LRP5) mutation and a homozygous methylenetetrahydrofolate reductase (MTHRF) polymorphism. JBMR. 2014;29 (4): 922-8.

Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease Type C: a final report of the NPC Registry

BackgroundNiemann-Pick disease Type C (NP-C) is a rare, progressive neurodegenerative disorder characterized by progressive neurodegeneration and premature death. We report data at closure of the NPC Registry that describes the natural history, disease course and treatment experience of NP-C patients in a real-world setting.MethodsThe NPC Registry was a prospective observational cohort study that ran between September 2009 and October 2017. Patients with a confirmed diagnosis of NP-C were enrolled regardless of treatment status. All patients underwent clinical assessments and medical care as determined by their physicians; data were collected through a secure internet-based portal.ResultsAt closure on October 19, 2017, 472 patients from 22 countries were enrolled in the NPC Registry. Mean (standard deviation) age at enrollment was 21.2 (15.0) years, and 51.9% of patients were male. First neurological symptom onset occurred during the early-infantile (< 2 years), late-infantile (2 to < 6 years), juvenile (6 to < 15 years), or adolescent/adult (≥ 15 years) periods in 13.5, 25.6, 31.8, and 29.1% of cases, respectively. The most frequent neurological manifestations prior to enrollment included ataxia (67.9%), vertical supranuclear gaze palsy (67.4%), dysarthria (64.7%), cognitive impairment (62.7%), dysphagia (49.1%), and dystonia (40.2%). During infancy, splenomegaly and hepatomegaly were frequent (n = 199/398 [50%] and n = 147/397 [37.0%], respectively) and persisted in most affected patients. Of the 472 enrolled patients, 241 were continuously treated with miglustat during the NPC Registry observation period, of whom 172 of these 241 patients were treated continuously for ≥12 months. A composite disability score that assesses impairment of ambulation, manipulation, language, and swallowing was highest in the early-infantile population and lowest in the adolescent/adult population. Among the continuous miglustat therapy population, 70.5% of patients had improved or had stable disease (at least 3 of the 4 domains having a decreased or unchanged score between enrollment and last follow-up). The NPC Registry did not identify any new safety signals associated with miglustat therapy.ConclusionsThe profiles of clinical manifestations in the final NPC Registry dataset agreed with previous clinical descriptions. Miglustat therapy was associated with a stabilization of neurological manifestations in most patients. The safety and tolerability of miglustat therapy was consistent with previous reports.

Role of Ligamentum Flavectomy in Lumbar Spinal Canal Stenosis

Background: Lumbar spinal canal stenosis (LSCS) is a degenerative condition in which changes in the discs, ligamentum flavum, and facet joints with aging cause narrowing of the spaces around the neurovascular structures of the spine. These changes lead to pain in the legs and back, as well as impaired ambulation and other disabilities. Objective: To provide an update review for determining the role of ligamentum flavectomy in lumbar spinal canal stenosis. Patients and methods: This study was carried out as an interventional prospective study on 23 patients with lumbar spinal canal stenosis from August 2018 till August 2019. Study was conducted in Orthopedic Surgery Departments, EL-Sayed Galal and EL-Haram specialized Hospitals and aimed at assessment of the role of ligamentum flavectomy in lumbar spinal canal stenosis. Results: The mean age was 50.5 ± 5.7 years ranging from 41 to 59 years. According to gender distribution, they were 13(56.5 %) males, and 10 (43.5%) females. The preoperative VAS ranged between 5-9 with mean 6.8 ±1.4. Six weeks after operation its range became 1-5 with mean 2.8 ±0.98. Twelve weeks later, the range was 1-3 with mean 1.7 ±0.7. The preoperative ODI ranged between 3-46 with mean 19.56 ±19.65. Six weeks later, the range between 1-18 with mean 7.3 ±7.26. At twelve weeks, the range was between 1-15 with mean 4.2 ± 8.86. At level L4/L5, ten patients (43.48%) have lumbar stenosis. At L3/L4 and L4/L5 levels seven patients (30.42%), and at L2/L3, L3/L4, L4/L5 levels six patients (26.1%) have stenosis. Conclusion: Ligamentum flavum hypertrophy is one of main causes of spinal canal stenosis so ligamentum flavectomy is an essential step in all surgical management of lumbar spinal canal stenosis for decompression of spinal canal.

Role of Ligamentum Flavectomy in Lumbar Spinal Canal Stenosis

Background: Lumbar spinal canal stenosis (LSCS) is a degenerative condition in which changes in the discs, ligamentum flavum, and facet joints with aging cause narrowing of the spaces around the neurovascular structures of the spine. These changes lead to pain in the legs and back, as well as impaired ambulation and other disabilities. Objective: To provide an update review for determining the role of ligamentum flavectomy in lumbar spinal canal stenosis. Patients and methods: This study was carried out as an interventional prospective study on 23 patients with lumbar spinal canal stenosis from August 2018 till August 2019. Study was conducted in Orthopedic Surgery Departments, EL-Sayed Galal and EL-Haram specialized Hospitals and aimed at assessment of the role of ligamentum flavectomy in lumbar spinal canal stenosis. Results: The mean age was 50.5 ± 5.7 years ranging from 41 to 59 years. According to gender distribution, they were 13(56.5 %) males, and 10 (43.5%) females. The preoperative VAS ranged between 5-9 with mean 6.8 ±1.4. Six weeks after operation its range became 1-5 with mean 2.8 ±0.98. Twelve weeks later, the range was 1-3 with mean 1.7 ±0.7. The preoperative ODI ranged between 3-46 with mean 19.56 ±19.65. Six weeks later, the range between 1-18 with mean 7.3 ±7.26. At twelve weeks, the range was between 1-15 with mean 4.2 ± 8.86. At level L4/L5, ten patients (43.48%) have lumbar stenosis. At L3/L4 and L4/L5 levels seven patients (30.42%), and at L2/L3, L3/L4, L4/L5 levels six patients (26.1%) have stenosis. Conclusion: Ligamentum flavum hypertrophy is one of main causes of spinal canal stenosis so ligamentum flavectomy is an essential step in all surgical management of lumbar spinal canal stenosis for decompression of spinal canal.

Physical Activity and Mortality among Male Survivors of Myocardial Infarction.

An inverse association between physical activity (PA) and risk of CHD has been seen in many studies, but evidence for benefits of PA after myocardial infarction (MI) in reducing mortality is limited. Using data from the Health Professionals Follow-up Study cohort, we followed male survivors of MI. Short- and long-term changes in PA from before to after MI were calculated, and participants without ambulation impairment were classified into maintained low, decreased, increased, or maintained high PA categories. Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality across PA and PA change categories. During a mean of 14 yr of follow-up of 1651 incident nonfatal MI cases, we documented 678 deaths, 307 were due to cardiovascular disease. The adjusted HR for all-cause mortality comparing ≥21 with ≤1.5 MET·wk of PA before MI was 0.73 (95% CI = 0.59-0.89, Ptrend = 0.03). Compared with men who maintained low PA before and after MI, men who maintained high PA had a 39% (95% CI = 25-50) lower risk of all-cause mortality, and those who had a long-term increase in PA from before to after MI had a 27% (95% CI = 6-43) lower risk. Walking for ≥30 min·d after MI was associated with a 29% lower mortality (HR = 0.71, 95% CI = 0.58-0.84), independent of walking pace, and walking pace after MI was inversely associated with mortality (HR = 0.67, 95% CI = 0.49-0.92). Maintaining a high PA or having a long-term increase in PA from before to after MI was associated with lower mortality among male MI survivors. Walking time and walking pace after MI were each inversely associated with mortality.

Intervention to decrease leaving without treatment among intoxicated emergency department patients

ObjectiveApproximately 15% of the >4000 patients presenting each year to our emergency department (ED) with a chief complaint or discharge diagnosis related to alcohol were leaving without treatment (LWT). If they are not clinically sober at the time of departure, these patients are at risk for falls or other injury. Our goal was to create an intervention to decrease this rate of early departure. MethodsA stakeholder group identified the reasons why intoxicated patients were leaving without treatment, concluding that the primary reason patients left was there was no process in place for evaluating and caring for these patients who potentially had impaired decision-making capacity. The group created a worksheet for the triage nurse to identify and manage patients presenting with intoxication and impaired decision-making or ambulation, with protocols to keep the patient in a supervised area. We performed a before and after analysis, evaluating 12 months before and 12 months after the protocol was initiated, with the primary outcome being the rate of intoxicated patients who left without treatment. We also measured the recidivism rate (the rate of return to the ED within 24 h after departure) and the ED length of stay (LOS). ResultsAfter the intervention was initiated, the percentage of intoxicated patients who left without treatment decreased from 15.0% to 7.4% LWT (p < 0.001). Among patients who stayed until discharge during the intervention period, the 24-hour recidivism was 9.4%, compared to 22.6% for those who left without treatment (p < 0.001). This difference in recidivism rates for each group was the same before and after the intervention, but fewer patients left without treatment after. For those patients with alcohol-related visits, the ED LOS was statistically significantly longer in the intervention phase, by a mean of 42 min for all patients (p < 0.001), as well as by a mean of 24 min for those who stayed to be dispositioned (p = 0.031). ConclusionProviding a standardized process for caring for acutely intoxicated patients leads to fewer patients leaving the ED before discharge. Patients who stay to the completion of treatment have a lower recidivism rate within 24 h after leaving than those in the leaving without treatment category.

163 Thai Traditional Game-Based Exercise for Gait and Balance of People with Parkinson's Disease

Abstract Falls and recurrent falls are serious complications for people with PD. Poor standing balance, impaired ambulation, impaired lower-limb motor planning, postural instability and falling in previous year are associated with falling in PD. Exercise based computer game (Exergaming) have been used for motor rehabilitation to promote gait and balance and can encourage therapeutic activity. However, many commercially available games are not affordable for some people with Parkinson’s Disease. The aim of this study was to evaluate the effectiveness of Thai Traditional game (TTG) based exercise on gait and balance in people with Parkinson’s Disease. A total of 22 participants with PD (mild –moderate severity) were randomly assigned to either a TTG group or a control group. Participants in TTG completed 1 hour, 3 sessions a week for 10 weeks. The TTG comprises 10 games involved instruction in sit to standing, slow and fast walking speed, turning, weight shifting, reaching, obstacle stepping, cognition, clapping and singing. Gait and balance were assessed before and after the training sessions. Measures included the Berg Balance Scale (BBS), Balance platform, Timed Up and Go (TUG) and The GaitRite walkway. Participants in TTG groups showed significantly improved BBS, TUG, gait velocity and sagittal mean sway with eyes open (p &amp;lt;0.05). Thai Traditional Game based exercise incorporated therapeutic movement could lead improvement in gait and balance and participants seem to enjoy playing as an activity while maintaining their functionality. Future studies should incorporate larger groups and focus on long-term compliance and follow-up.

109 Thai Traditional Game-Based Exercise for Gait and Balance of People with Parkinson's Disease

Abstract Falls and recurrent falls are serious complications for people with PD. Poor standing balance, impaired ambulation, impaired lower-limb motor planning, postural instability and falling in previous year are associated with falling in PD. Exercise based computer game (Exergaming) have been used for motor rehabilitation to promote gait and balance and can encourage therapeutic activity. However, many commercially available games are not affordable for some people with Parkinson ’s disease. The aim of this study was to evaluate the effectiveness of Thai Traditional game (TTG) based exercise on gait and balance in people with Parkinson ’s disease. A total of 22 participants with PD (mild –moderate severity) were randomly assigned to either a TTG group or a control group. Participants in TTG completed 1 hour, 3 sessions a week for 10 weeks. The TTG comprises 10 games involved instruction in sit to standing, slow and fast walking speed, turning, weight shifting, reaching, obstacle stepping, cognition, clapping and singing. Gait and balance were assessed before and after the training sessions. Measures included the Berg Balance Scale (BBS), Balance platform, Timed Up and Go (TUG) and The GaitRite walkway. Participants in TTG groups showed significantly improved BBS, TUG, gait velocity and sagittal mean sway with eyes open (p &amp;lt;0.05). Thai Traditional Game based exercise incorporated therapeutic movement could lead improvement in gait and balance and participants seem to enjoy playing as an activity while maintaining their functionality. Future studies should incorporate larger groups and focus on long-term compliance and follow-up.

Responder rates to fampridine differ between clinical subgroups of MS patients and patient reported outcome influences treatment decision making

BackgroundFampridine is an effective treatment to improve ambulation for some multiple sclerosis (MS) patients. Remarkable discrepancies exist between responder rates in clinical trials and the proportion of patients continuing treatment in clinical practice. This may be related to clinical phenotypes of MS patients, and the influence of patient reported outcome (PRO) on treatment decision making. ObjectiveTo analyse responder rates to fampridine on ambulation and upper extremity function (UEF) and the influence on treatment decision making in different clinical subgroups in a real-world setting. MethodsMS patients with ambulatory impairment treated with fampridine were included. Patients were subdivided based on disease duration, clinical phenotype, Expanded Disability Status Scale (EDSS), baseline walking speed, and presence of UEF impairment. Ambulatory response was assessed with the Timed 25-Foot Walk (T25FW, responder defined as ≥20% improvement) and with the MS Walking Scale (MSWS, responder defined as ≥8 points improvement) as a PRO. For patients also reporting impaired UEF, the Arm Function in MS Questionnaire (AMSQ, responder defined as ≥15 improvement) was the PRO of choice. Decision on treatment continuation was based on improvement of T25FW, MSWS and the clinicians’ overall impression for improvement. ResultsIn total 344 patients were included of which 75.3% continued treatment. More patients with a relapsing clinical phenotype continued treatment vs patients with a progressive phenotype (83.6 vs 68.6%, p < 0.01).A positive linear trend was found between severity of walking disability, as determined by baseline walking speed, and T25FW response (p < 0.01), while there was an inverse linear association between walking disability and MSWS response (p = 0.03). However, the proportion of patients continuing treatment was similar between subgroups of baseline walking speed. Impaired UEF was reported by 183 (66.5%) patients, of which 64 (39.3%) were AMSQ responders. Patients responding on AMSQ compared to non-responders, were also more frequently MSWS responders (82.8 vs 65.3%, p = 0.02), while response on T25FW was similar, and continued treatment more often (85.9 vs 70.7%, p = 0.04). This suggests an influence of PRO on treatment decision making. ConclusionResponder rates and treatment continuation of fampridine differed between clinical subgroups of MS. PROs influenced treatment decision making of fampridine in clinical practice, particularly in patients with mild ambulatory impairment or those reporting UEF impairment. To some extent, these findings explain discrepancies found between clinical trials and clinical practice, and support the importance of subgroup analyses and incorporation of PROs in clinical trials. For clinical practice, using PROs to assess patients experience in conjunction with performance measures helps in treatment decision making.

Preoperative Narcotic Use, Impaired Ambulation Status, and Increased Intraoperative Blood Loss Are Independent Risk Factors for Complications Following Posterior Cervical Laminectomy and Fusion Surgery.

ObjectiveThis retrospective cohort study seeks to identify risk factors associated with complications following posterior cervical laminectomy and fusion (PCLF) surgery. MethodsAdults undergoing PCLF from 2012 through 2018 at a single center were identified. Demographic and radiographic data, surgical characteristics, and complication rates were compared. Multivariate logistic regression models identified independent predictors of complications following surgery. ResultsA total of 196 patients met the inclusion criteria and were included in the study. The medical, surgical, and overall complication rates were 10.2%, 23.0%, and 29.1% respectively. Risk factors associated with medical complications in multivariate analysis included impaired ambulation status (odds ratio [OR], 2.27; p=0.02) and estimated blood loss over 500 mL (OR, 3.67; p=0.02). Multivariate analysis revealed preoperative narcotic use (OR, 2.43; p=0.02) and operative time (OR, 1.005; p=0.03) as risk factors for surgical complication, whereas antidepressant use was a protective factor (OR, 0.21; p=0.01). Overall complication was associated with preoperative narcotic use (OR, 1.97; p=0.04) and higher intraoperative blood loss (OR, 1.0007; p=0.03). ConclusionPreoperative narcotic use and estimated blood loss predicted the incidence of complications following PCLF for CSM. Ambulation status was a significant predictor of the development of a medical complication specifically. These results may help surgeons in counseling patients who may be at increased risk of complication following surgery.

Trastorno del espectro de la neuromielitis óptica

El síndrome de Devic, también conocido como trastorno del espectro de la neuromielitis óptica (NMOSD, por sus sigla en inglés), es considerado una enfermedad inflamatoria, desmielinizante y autoinmune del sistema nervioso central que afecta en su mayoría los nervios ópticos, el quiasma óptico y la médula espinal. Si bien en algunos casos se puede simular un cuadro clínico similar a esclerosis múltiple, hoy en día se conocen aspectos imagenológicos, inmunológicos y patológicos que permiten establecer las diferencias entre estas dos entidades.&#x0D; Se presenta el caso de una mujer adulta mayor con antecedente de síndrome de Sjögren en manejo ambulatorio con corticoide y azatioprina, quien ingresa por cuadro clínico de mes y medio de evolución consistente en disestesias de predominio en miembros inferiores, alteración de la marcha y compromiso visual. Ante el compromiso neurológico, se decide realizar imágenes diagnósticas y perfil inmunológico, con reportes de resonancia magnética nuclear cervical y torácica con contraste que evidencian mielitis multifocal por compromiso cervical y torácico a nivel de C4 en T7-T8 con hiperdensidad centromedular sin realce, además de autoanticuerpos séricos dirigidos contra el canal acuaporínico (AQP4) positivos, dando así el diagnóstico de NMOSD.&#x0D; Se inició manejo con pulsos de metilprednisolona concomitantemente con plasmaféresis completando cinco sesiones. Sin embargo, ante la persistencia del cuadro clínico se inició manejo con un agente biológico selectivo que bloquea la actividad de los linfocitos B tipo rituximab con resolución parcial de los síntomas. Se discute, además, la evolución clínica e imagenológica de este caso ejemplar, así como los avances más notables en el diagnóstico y manejo.

Predicting Ambulatory Function Based on Infantile Lower Extremity Posture Types in Amyoplasia Arthrogryposis.

Arthrogryposis multiplex congenita (AMC) is a nonprogressive syndrome with multiple rigid joints, fibrotic periarticular tissue, and muscular fibrosis. The most common subgroup is amyoplasia. Ambulation is one of the most significant functions of the lower extremities as it translates to increased functionality and independence in adulthood. There is no predicative scale to determine ambulation at maturity for the infant with amyoplasia. It is believed lower extremity resting position of infants with amyoplasia potentially correlates with ambulation at maturity. The purpose of this study was to classify the infantile position of lower extremities and muscle strength to predict ambulation potential at maturity. Children with amyoplasia were retrospectively reviewed and classified into groups based on infantile position of hip-knee alignment and limb muscle function. Sitting, standing, and walking skills from infancy into adulthood were evaluated. The ambulation function was correlated with the infantile position of the lower extremities. Amyoplasia cases were sorted into 5 types and correlated with ambulatory potential. Type I: mild ambulatory impairment with infantile position of flexed knees and hips but full range of motion. At maturity, all were community ambulators. Type II: moderate ambulatory impairment having infantile position of hip flexion, hip external rotation, and knee flexion contractures. Hip abductors and external rotators had antigravity strength. All stood and walked during the first decade of life with knee ankle foot orthoses. Type III: severe ambulatory impairment having infantile position of hip flexion, abduction, external rotation, and knee flexion contractures but lacked hip muscle recruitment. All used wheelchairs at maturity. Type IV: mild ambulatory impairment with infantile position of extended knees and flexed dislocated hips. At maturity, 90% were community ambulators. Type V: variable ambulatory impairment having asymmetric hip and knee alignment with unilateral hip dysplasia with extended knee and opposite limb flexed. Ambulation skill varied at maturity with 27% full-time wheelchair users. Amyoplasia can be sorted by infantile position of lower extremities and muscle strength into 5 types to predict ambulatory function. Level III-Prognostic Study.

Disability and Therapeutic Response in Paediatric Neuromyelitis Optica Spectrum Disorder: A Case Series from Iran.

The characteristics ofpaediatric neuromyelitis optica spectrum disorder (NMOSD) may indicate the degree of disability and identify factors that predict the response to treatment. Among 114 NMOSD patients in an acquired demyelinating syndromes registry at the Sina Hospital, in Tehran, Iran, 10 paediatric NMOSD patients with longitudinal follow-up from 2005 to 2016 were retrospectively identified. The median time between disease onset and diagnosis was 18 months (range 1-108 months). All patients had a relapsing course, which resulted in disability in six with severe visual impairment and functional blindness in one and impaired ambulation in five patients during follow-up. Azathioprine (AZA) was first drug of choice for prophylaxis, but in five patients new attacks occurred and therapy was switched to rituximab (RTX) with no further relapses after median two years (range 1-3 y) follow-up. Paediatric onset of NMOSD was associated with severe attacks and poor response in 50 % of cases to AZA, RTX seemed to decrease the relapse rate.

P.071 Clinical and demographic predictors of stress in parents of children with genetically determined leukoencephalopathies

Background: Genetically-determined leukoencephalopathies comprise a rare group of inherited white matter disorders. The vast majority are associated with a progressive disease course and early death. This study seeks to determine the clinical and demographic correlates of stress in parents of leukodystrophy patients, for future clinical guidance. Methods: A cross-sectional study including 36 families was performed. Children aged 1 month to 12 years with a diagnosed leukodystrophy or genetically-determined leukoencephalopathy were included. 31 mothers and 24 fathers completed the Parental Stress Index, 4th edition (PSI-4). One demographic questionnaire was completed per family. Clinical data was gathered within 6 months of the questionnaires. Statistical analysis was performed with total stress (TS) scores as the primary outcome. Results: Mothers and fathers had comparable TS scores. No clinical or demographic factors predicted the father’s TS score. Greater ambulatory impairment, using the GMFCS scale, correlated to lower TS scores in the mother. Conclusions: The progressive nature of these conditions makes it such that anticipating a child’s inability to walk may cause more stress for mothers than a child’s actual inability to ambulate. The inability of all other variables to predict total stress highlights a need for individualized approaches when addressing stress in these families.

18 F-NaF PET/CT IMAGING IN FIBROUS DYSPLASIA OF BONE.

Fibrous dysplasia (FD) is a mosaic skeletal disorder resulting in fractures, deformity, and functional impairment. Clinical evaluation has been limited by a lack of surrogate endpoints capable of quantitating disease activity. The purpose of this study was to investigate the utility of 18 F-NaF PET/CT imaging in quantifying disease activity in patients with FD. Fifteen consecutively evaluated subjects underwent whole-body 18 F-NaF PET/CT scans, and FD burden was assessed by quantifying FD-related 18 F-NaF activity. 18 F-NaF PET/CT parameters obtained included (i) SUVmax (standardized uptake value [SUV] of the FD lesion with the highest uptake); (ii) SUVmean (average SUV of all 18 F-NaF-positive FD lesions); (iii) total volume of all 18 F-NaF-positive FD lesions (TV); and (iv) total FD lesion activity determined as the product of TV multiplied by SUVmean (TA = TV × SUVmean ) (TA). Skeletal outcomes, functional outcomes, and bone turnover markers were correlated with 18 F-NaF PET/CT parameters. TV and TA of extracranial FD lesions correlated strongly with skeletal outcomes including fractures and surgeries (p values ≤ 0.003). Subjects with impaired ambulation and scoliosis had significantly higher TV and TA values (P < 0.05), obtained from extracranial and spinal lesions, respectively. Craniofacial surgeries correlated with TV and TA of skull FD lesions (P < 0.001). Bone turnover markers, including alkaline phosphatase, N-telopeptides, and osteocalcin, were strongly correlated with TV and TA (P < 0.05) extracted from FD lesions in the entire skeleton. No associations were identified with SUVmax or SUVmean . Bone pain and age did not correlate with 18 F-NaF PET/CT parameters. FD burden evaluated by 18 F-NaF-PET/CT facilitates accurate assessment of FD activity, and correlates quantitatively with clinically-relevant skeletal outcomes. © 2019 American Society for Bone and Mineral Research.

Angiogenic Factor AGGF1-Primed Endothelial Progenitor Cells Repair Vascular Defect in Diabetic Mice.

Hyperglycemia-triggered vascular abnormalities are the most serious complications of diabetes mellitus (DM). The major cause of vascular dysfunction in DM is endothelial injury and dysfunction associated with the reduced number and dysfunction of endothelial progenitor cells (EPCs). A major challenge is to identify key regulators of EPCs to restore DM-associated vascular dysfunction. We show that EPCs from heterozygous knockout Aggf1+/- mice presented with impairment of proliferation, migration, angiogenesis, and transendothelial migration as in hyperglycemic mice fed a high-fat diet (HFD) or db/db mice. The number of EPCs from Aggf1+/- mice was significantly reduced. Ex vivo, AGGF1 protein can fully reverse all damaging effects of hyperglycemia on EPCs. In vivo, transplantation of AGGF1-primed EPCs successfully restores blood flow and blocks tissue necrosis and ambulatory impairment in HFD-induced hyperglycemic mice or db/db mice with diabetic hindlimb ischemia. Mechanistically, AGGF1 activates AKT, reduces nuclear localization of Fyn, which increases the nuclear level of Nrf2 and expression of antioxidative genes, and inhibits reactive oxygen species generation. These results suggest that Aggf1 is required for essential function of EPCs, AGGF1 fully reverses the damaging effects of hyperglycemia on EPCs, and AGGF1 priming of EPCs is a novel treatment modality for vascular complications in DM.

Association of Continuous Assessment of Step Count by Remote Monitoring With Disability Progression Among Adults With Multiple Sclerosis

ImportanceDisability measures in multiple sclerosis (MS) fail to capture potentially important variability in walking behavior. More sensitive and ecologically valid outcome measures are needed to advance MS research.ObjectivesTo assess continuous step count activity remotely among individuals with MS for 1 year and determine how average daily step count is associated with other measures of MS disability.Design, Setting, and ParticipantsIn a prospective longitudinal observational cohort study, 95 adults with relapsing or progressive MS who were able to walk more than 2 minutes with or without an assistive device were recruited between June 15, 2015, and August 8, 2016, and remotely monitored in their natural environment for 1 year. Patients were excluded if they had a clinical relapse within 30 days or comorbidity contributing to ambulatory impairment. Longitudinal analysis was performed from October 2017 to March 2018. Revised analysis was performed in December 2018.InterventionActivity monitoring of step count using a wrist-worn accelerometer.Main Outcomes and MeasuresAverage daily step count compared with in-clinic assessments and patient-reported outcomes.ResultsOf the 95 participants recruited (59 women and 36 men; mean [SD] age, 49.6 [13.6] years [range, 22.0-74.0 years]), 35 (37%) had progressive MS, and the median baseline Expanded Disability Status Scale score was 4.0 (range, 0-6.5). At 1 year, 79 participants completed follow-up (83% retention). There was a modest reduction in accelerometer use during the 1 year of the study. A decreasing average daily step count during the study was associated with worsening of clinic-based outcomes (Timed 25-Foot Walk, β = −13.09; P < .001; Timed-Up-and-Go, β = −9.25; P < .001) and patient-reported outcomes (12-item Multiple Sclerosis Walking Scale, β = −17.96; P < .001). A decreasing average daily step count occurred even when the Expanded Disability Status Scale score remained stable, and 12 of 25 participants (48%) with a significant decrease in average daily step count during the study did not have a reduction on other standard clinic-based metrics. Participants with a baseline average daily step count below 4766 (cohort median) had higher odds of clinically meaningful disability (Expanded Disability Status Scale score) worsening at 1 year, adjusting for age, sex, and disease duration (odds ratio, 4.01; 95% CI, 1.17-13.78; P = .03).Conclusions and RelevanceContinuous remote activity monitoring of individuals with MS for 1 year appears to be feasible. In this study, a decreasing average daily step count during a 1-year period was associated with worsening of standard ambulatory measures but could also occur even when traditional disability measures remained stable. These results appear to support the prospect of using the average daily step count as a sensitive longitudinal outcome measure in MS and as a clinically relevant metric for targeted intervention.

Dalfampridine benefits ambulation but not cognition in multiple sclerosis

Background: Impaired cognition and ambulation are common in multiple sclerosis (MS). Dalfampridine is the first Food and Drug Administration (FDA)–approved medication to treat impaired ambulation in MS. Dalfampridine may benefit patients with cognitive impairment, given its effects on saltatory conduction and the association between cognitive and motor function. Objective: To examine the effects of dalfampridine on cognition in MS. To determine if the anticipated improved cognition is grounded in dalfampridine’s effects on ambulation. Methods: Adults with MS were randomized to dalfampridine (n = 45) or placebo (n = 16) for 12 weeks. Cognition and motor function were assessed at baseline and end-point. Results: T25FW and 6-minute walk (6MW) performance improved at end-point in the treatment group but not in the placebo group (p < 0.05). Our primary outcome, performance on the Symbol Digit Modalities Test, did not improve. About 30% (n = 12) of the dalfampridine group demonstrated ⩾20% improved ambulation and were categorized “responders.” Among “responders”, Symbol Digit Modalities test performance did not improve. However, performance on the Paced Auditory Serial Addition Test improved among “responders” (p < 0.05). Conclusion: Dalfampridine benefits timed ambulation but not cognition. Some improvement among ambulation “responders” is consistent with prior reports of cognition-motor coupling in MS (ClinicalTrials.gov#: NCT02006160).