Adaptation to repeated gait-slip perturbations among individuals with multiple sclerosis.

BACKGROUND: Perturbation training, built upon motor adaptation and learning, has been increasingly used as a fall prevention paradigm in older adults. This training paradigm involves repeated externally-induced perturbations (like slips) to facilitate the error-driven learning of necessary motor skills for preventing falls. It remains unknown if people with multiple sclerosis can adapt to large-scale slip perturbations, which impedes the application of perturbation training in persons with multiple sclerosis. This study explored whether people with multiple sclerosis can adapt to large-scale repeated gait-slips. METHODS: Thirteen individuals with multiple sclerosis (the mean ± standard deviation of the Patient Determined Disability Steps: 2.27 ± 1.42) were exposed unexpectedly to a block of five repeated standard slips while walking on a treadmill. The outcome (fall or recovery) for each slip, as our primary outcome measure, was determined. A battery of secondary variables, including dynamic gait stability and gait parameters, were also calculated. Both primary and secondary variables were compared across trials. RESULTS: Our participants showed a rapidly reduced slip-fall rate (from 92.3% on the first slip to 30.8% on the fifth, p < 0.001). They mainly adopted proactive, assisted by reactive, strategies to improve dynamic gait stability, thus reducing the risk of slip-falls. The proactive adjustments, including shortened step, reduced foot landing angle, and flexed knee, shifted the center of mass anteriorly to be closer to the base of support. Such changes in center of mass position improved dynamic gait stability before the slip. Dynamic gait stability after the slip was also improved across trials, as a reactive strategy. CONCLUSION: With practice, people with multiple sclerosis can adapt to large-scale, high-speed, gait-slips and acquire necessary skills against falls. Such skills primarily involve proactive strategy which is assisted by reactive strategy. The proactive strategy would shift the body's center of mass closer to the base of support, improving dynamic gait stability and reducing falls. Our findings could provide a theoretical foundation for deploying perturbation training to prevent falls in people with multiple sclerosis.

Relative importance of physical and psychological factors to slowness in people with mild to moderate multiple sclerosis.

BACKGROUND: Mobility impairment is common in people with multiple sclerosis (MS). Gait speed has shown strong correlations with other mobility measures in MS. The purpose of this study was to assess the relative importance of a battery of factors in determining gait speed among people with MS. METHODS: Thirty-one individuals with MS (the mean (standard deviation) of the Patient Determined Disability Steps: 3.68(1.70)) participated in this cross-sectional observational study. Their gait speed was assessed using the Timed-25-Foot Walking test. Six factors which could slow gait speed in MS, including the strength capacity at knee joints, functional mobility, body balance, dorsiflexion range of motion of ankle joints, bilateral foot cutaneous sensation level, and the fear of falling, were also assessed. Multiple regression and relative weight analysis were used to identify the relative importance of each factor in explaining the gait speed variation. RESULTS: All six factors together accounted for about 86% of the observed variation in gait speed; each explaining a statistically significant amount. The most important factor was the strength measurement (relative weight = 0.321) which accounted for 37.2% of the explained variation in gait speed. CONCLUSION: Muscle strength, particularly the knee joint strength capacity, could be a principal factor determining gait speed in people with mild to moderate MS. Other factors also significantly affect gait speed in this population. The findings from this study could provide guidance in terms of prioritizing actions to improve gait speed in people with MS.

Timing of diagnosis of 47,XXY and 48,XXYY: a survey of parent experiences.

47,XXY/Klinefelter syndrome is the most common sex chromosomal aneuploidy, yet 64% of males with this condition go undiagnosed. 48,XXYY is less common and there is less known about the diagnosis. The objective of this study is to describe the diagnosis experiences of parents of males with 47,XXY and 48,XXYY. Parents of 89 males with 47,XXY and 76 males with 48,XXYY completed a survey that gathered data about their experiences leading to a diagnosis, including the current age of the child, age at diagnosis, reasons for initial concern, and the specialists providing the diagnosis. In the 47,XXY cohort diagnosed postnatally, 59% presented with developmental delay, with a mean age at first parental concern of 5.2 years and mean age of diagnosis at 10.0 years. The remaining 41% presented with endocrinologic issues with a mean age at first concern of 19.1 years and mean age of diagnosis at 21.1 years. In the 48,XXYY group, 93% presented with developmental delay, with mean age at first parental concern of 2.4 years and mean age of diagnosis at 7.6 years. Hence, the average time from initial parental concern to diagnosis of 47,XXY or 48,XXYY ranges from 2 to 5 years, with those presenting with developmental issues having a longer lag to diagnosis compared to those presenting with endocrinologic issues. Increased awareness of the developmental, psychological, and medical features of 47,XXY and 48,XXYY is important to facilitate timely diagnosis and initiation of appropriate screenings and treatments that are important for optimal outcomes.

Olfactory dysfunction in fragile X tremor ataxia syndrome.

INTRODUCTION: We investigated olfactory defects in fragile X-associated tremor/ataxia syndrome (FXTAS), a finding reported on in other neurodegenerative disorders with clinical features that overlap those of FXTAS. METHODS: We measured olfactory identification capacity in 41 FMR1 premutation carriers and 42 controls using the University of Pennsylvania Smell Identification Test (UPSIT). Carriers received neurologic evaluations using motor rating scales for tremor, ataxia, and parkinsonism. Cognitive function was measured using the Montreal Cognitive Assessment test. RESULTS: Frequency of olfactory defects was higher in carriers, compared to controls (61% versus 29%; P = 0.003). There was no statistically significant group difference in severity of olfaction defects, after accounting for differences in age, and in rates of head injury and smoking. However, both the frequency (odds ratio = 3.9; 95% confidence interval: 0.81-19.1) and severity (28.6 versus 33.4; P = 0.01) of these defects were greater in cognitively impaired, compared to cognitively intact, carriers. There was no correlation between UPSIT scores and the above-mentioned motor rating scales. CONCLUSIONS: FMR1 premutation carriers are susceptible to olfactory identification defects. The severity of these defects is comparable to that reported in hereditary ataxias, but less than that in PD and Alzheimer's disease. This concurrence across neurodegenerative disorders suggests a shared system vulnerability that correlates with, but is not limited to, cognitive impairment, because it is also found in cognitively intact carriers. These results need to be corroborated in a larger prospective study of FMR1 premutation carriers that extends beyond olfactory identification to include measures of smell thresholds.

New clinical findings in the fragile X-associated tremor ataxia syndrome (FXTAS).

The objective of this paper was to assess the phenotypic variance in patients with the Fragile X-associated Tremor Ataxia Syndrome (FXTAS) and to further elucidate genotype-phenotype correlations in the illness. A second goal was to generate hypotheses regarding symptom progression based on careful histories in our sample that can now be tested in ongoing longitudinal studies. The variability of clinical signs and symptom progression in FXTAS complicates our understanding of its phenotype and presents a series of problems in clinical trial design. Similarly, pre-motor and non-motor symptoms have not been adequately explored to answer outstanding questions regarding genotype-phenotype associations in FXTAS. This was a cross-sectional study of FMR1 premutation carriers from known fragile X syndrome pedigrees. We report on the first 50 subjects who have completed a full neurologic evaluation and a brain MRI. Subjects were selected on the basis of motor symptoms or abnormal results (>1 SD) on a quantitative instrument designed to detect mild tremor and ataxia (CATSYS 1994). A neuropsychological battery included the WAIS-III, COWA, and WCST. Statistical analysis used ANOVA and Fisher's exact test with p < 0.05. All FMR1 premutation carriers were men of mean age 65 ± 7 years. According to the diagnostic criteria of Jacquemont et al. (Am J Hum Genet 72(4):869-878, 2003), 21 subjects met criteria for definite FXTAS, 10 for probable, 9 for possible, and 10 were indeterminate. Duration of motor symptoms was significantly longer in the definitive group (8.6 ± 6) compared to the other groups (p < 0.01). The presentations in 40 subjects, excluding the indeterminate group, included: tremor 24, ataxia 5, memory symptoms 3, parkinsonism 2, and torticollis 1. The data suggest at least two dominant phenotypic presentations: (a) a tremor-dominant subtype in which the onset of ataxia is delayed; (b) a second in which ataxia is the dominant presentation from the outset. In both subtypes, once ataxia emerges it tends to track frontal cognitive changes (p < 0.01). The data support the view that FXTAS is a late-life neurodegenerative disorder with involvement of motor, non-motor, and cognitive systems. The results suggest at least two presentations with tremor- and ataxia-predominant phenotypes. In both, global cognitive decline appears to track ataxia. Prospective longitudinal studies are needed to validate this proposed evolution of FXTAS and its relevance to future clinical trials design.