Overcoming clinical challenges of refractory neuropathic pain.

INTRODUCTION: Refractory neuropathic pain (ReNP), and its definition, is widely disputed among clinicians due in part to unclear diagnosing guidelines, overall duration of neuropathic pain, and the exhaustiveness of treatment options. Usually, ReNP is defined as chronic, intractable, and unresponsive neuropathic pain that has otherwise been untreatable. AREAS COVERED: In this narrative review, we discuss and summarize the effectiveness of prospective ReNP research conducted over the past 10 years. This research looks at pharmacological and interventional therapies in clinical trial settings. The pharmacological therapies discussed include the use of adjuvant treatments to improve the safety and efficacy of conventional approaches. Different modalities of administration, such as injection therapy and intrathecal drug delivery systems, provide targeted drug delivery. Interventional therapies such as neuromodulation, pulse radiofrequency, and nerve lesioning are more invasive; however, they are increasingly utilized in the field, as reflected in ongoing clinical trials. EXPERT OPINION: Based on the current data from RCTs and systematic reviews, it is clear that single drug therapy cannot be effective and has significant limitations. Transitioning to interventional modalities that showed more promising results sooner rather than later may be even more cost efficient than attempting different conservative treatments with a high failure rate.

Normative database of postural sway measures using inertial sensors in typically developing children and young adults.

OBJECTIVE: Reference values utilizing the APDM MobilityLab® inertial sensor system have not been established in children and young adults ages 5-30. These values are necessary for clinicians and researchers to compare to children with balance impairments. METHODS: A group of 144 typically developing children and young adults from age 5-30 years completed the instrumented SWAY test during 6 test conditions: normal stance, firm surface, eyes open (EO) and closed (EC); normal stance, foam surface, EO and EC; and tandem stance, firm surface, EO and EC. Selected variables for normative outcomes included total sway area, and the mean, sagittal and coronal values for RMS sway, jerk, sway velocity and path length. Sex differences were examined within age groups via t tests. The effect of age on postural sway variables was analyzed using a one-way ANOVA for the mean values of total sway area, RMS sway, velocity and jerk, followed by post-hoc pairwise comparisons. RESULTS: All sway parameters decreased significantly with age (p < 0.0001). Adult-like total sway area and jerk were achieved by ages 9-10 except for jerk during EC on foam. RMS sway and sway velocity reached adult levels by ages 11-13 during all EO and tandem stance conditions, and 14-21 with EC during normal stance on firm and foam surfaces for RMS sway and EC on firm surfaces for velocity. Females ages 5-6 performed more poorly during EO firm and EC foam for certain variables, but better during EO tandem and females ages 7-13 outperformed males when sex differences were found. SIGNIFICANCE: These reference values can now be used by clinicians and researchers to evaluate abnormal postural sway and response to interventions in children and young adults.

The Effects of Dual Task Cognitive Interference and Fast-Paced Walking on Gait, Turns, and Falls in Men and Women with FXTAS.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a genetic neurodegenerative disorder characterized by cerebellar ataxia, tremor, and cognitive dysfunction. We examined the impact of dual-task (DT) cognitive-motor interference and fast-paced (FP) gait on gait and turning in FXTAS. Thirty participants with FXTAS and 35 age-matched controls underwent gait analysis using an inertial sensor-based 2-min walk test under three conditions: (1) self-selected pace (ST), (2) FP, and (3) DT with a concurrent verbal fluency task. Linear regression analyses were performed to assess the association between FXTAS diagnosis and gait and turn outcomes. Correlations between gait variables and fall frequency were also calculated. FXTAS participants had reduced stride length and velocity, swing time, and peak turn velocity and greater double limb support time and number of steps to turn compared to controls under all three conditions. There was greater dual task cost of the verbal fluency task on peak turn velocity in men with FXTAS compared to controls. Additionally, stride length variability was increased and cadence was reduced in FXTAS participants in the FP condition. Stride velocity variability under FP gait was significantly associated with the number of self-reported falls in the last year. Greater motor control requirements for turning likely made men with FXTAS more susceptible to the negative effects of DT cognitive interference. FP gait exacerbated gait deficits in the domains of rhythm and variability, and increased gait variability with FP was associated with increased falls. These data may inform the design of rehabilitation strategies in FXTAS.

Prodromal Markers of Upper Limb Deficits in FMR1 Premutation Carriers and Quantitative Outcome Measures for Future Clinical Trials in Fragile X-associated Tremor/Ataxia Syndrome.

BACKGROUND: Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a rare, late-onset neurodegenerative disorder characterized by tremor and cerebellar gait ataxia, affecting premutation carriers (PMC) of CGG expansions (range, 55-200) in the fragile X mental retardation 1 (FMR1) gene. Discovery of early predictors for FXTAS and quantitative characterization of motor deficits are critical for identifying disease onset, monitoring disease progression, and determining efficacy of interventions. METHODS: A total of 39 PMC with FXTAS, 20 PMC without FXTAS, and 27 healthy controls performed a series of upper extremity (UE) motor tasks assessing tremor, bradykinesia, and rapid alternating movements that were quantified using an inertial-based sensor system (Kinesia One; Great Lakes NeuroTechnologies, Cleveland, OH, USA). Sub-scores from the clinician-rated FXTAS Rating Scale were correlated with the severity scores generated by the sensor system to determine its validity in FXTAS. RESULTS: PMC with FXTAS had significantly worse postural and kinetic tremor compared with PMC without FXTAS (P = 0.02, 0.03) and controls (P = 0.001, 0.0001), respectively, and slower finger tap (P = 0.001), hand movement (P = 0.0001), and rapid alternating movement speed (P = 0.003) and amplitude (P = 0.04) than controls. PMC without FXTAS had significantly worse right finger tap (P = 0.004), hand movement (P = 0.01), and rapid alternating movement speed (P = 0.003) and amplitude (P = 0.02) than controls. FXTAS Rating Scale subscores significantly correlated with all tremorography scores except for finger taps and left rapid alternating movement. CONCLUSIONS: These findings support the use of inertial sensor quantification systems as promising measures for preclinical FXTAS symptom detection in PMC, characterization of the natural history of FXTAS, assessment of medication responses, and outcome assessment in clinical trials.

Normative database of spatiotemporal gait parameters using inertial sensors in typically developing children and young adults.

BACKGROUND: Inertial sensors are increasingly useful to clinicians and researchers to detect gait deficits. Reference values are necessary for comparison to children with gait abnormalities. OBJECTIVE: To present a normative database of spatiotemporal gait and turning parameters in 164 typically developing children and young adults ages 5-30 utilizing the APDM Mobility Lab® system. METHODS: Participants completed the i-WALK test at both self-selected (SS) and fast as possible (FAP) walking speeds. Spatiotemporal gait and turning parameters included stride length, stride length variability, gait speed, cadence, stance, swing, and double support times, and foot strike, toe-off, and toe-out angles, turn duration, peak turn velocity and number of steps to turn. RESULTS: Absolute stride length and gait speed increased with age. Normalized gait speed, absolute and normalized cadence, and stride length variability decreased with age. Normalized stride length and all parameters of gait cycle phase and foot position remained unaffected by age except for greater FSA in children 7-8. Foot position parameters in children 5-6 were excluded due to aberrant values and high standard deviations. Turns were faster in children ages 5-13 and 7-13 in the SS and FAP conditions, respectively. There were no differences in number of steps to turn. Similar trends were observed in the FAP condition except: normalized gait speed did not demonstrate a relationship with age and children ages 5-8 demonstrated increased stance and double support times and decreased swing time compared to children 11-13 and young adults (ages 5-6 only). Females ages 5-6 demonstrated increased stride length variability in the SS condition; males ages 7-8 and 14-30 ha d increased absolute stride length in the FAP condition. Similarities and differences were found between our values and previous literature. SIGNIFICANCE: This normative database can be used by clinicians and researchers to compare abnormal gait patterns and responses to interventions.