Clinical case report of intractable paroxysmal sympathetic hyperactivity in TANGO2 deficiency disorder.

TANGO2 deficiency disorder (TDD) is a neurodegenerative disease characterized by a broad and variable spectrum of clinical manifestations, even among individuals sharing the same pathogenic variants. Here, we report a severely affected individual with TDD presenting with intractable paroxysmal sympathetic hyperactivity (PSH). While progressive brain atrophy has been observed in TDD, PSH has not been reported. Despite comprehensive workup for an acute trigger, no definite cause was identified, and pharmacological interventions were ineffective to treat PSH. Ultimately care was redirected to comfort measures. This article expands the clinical phenotype of patients with TDD, highlights the possibility of PSH in these patients, and the need for continued research for better treatments of TDD.

Six-Minute Walk as a Measure of Walking Capacity and Endurance in Patients With Pediatric-Onset Multiple Sclerosis.

BACKGROUND: Despite low levels of disability, youth with pediatric-onset MS (POMS) engage in less physical activity compared to peers. The contribution of walking capacity, endurance, behavior, and MS co-morbidities remain relatively undefined and may provide valuable insights into the limitations toward physical activity in youth with MS. OBJECTIVE: Investigate differences in walking capacity, endurance and real-world behaviors of daily activity between youth with POMS and controls. DESIGN/METHODS: Youth diagnosed with MS prior to 18 years and aged ≤21 years were recruited in addition to healthy controls. Subjects completed questionnaires to quantify fatigue, depression, and physical activity levels and the timed 2- and 6-minute walk (2MW, 6MW) as an assessment of walk capacity and endurance. Subjects were sent home with a waist-worn accelerometer to assess real-world walking behavior. RESULTS: Forty-five POMS and 85 control subjects were enrolled. The POMS cohort had a mean age of 16.9±2.7 years with a mean disease duration of 2.8±2.6 years. A greater proportion of the POMS cohort was overweight/obese compared to controls (60% versus 33%). Subjects with MS walked a significantly shorter distance in 6 minutes compared to controls (1848 feet vs 2134 feet, p<0.0001) and, unlike controls, were unable to accelerate to their peak speed at the end of the 6MW. BMI category and MS disease significantly impacted 6MW performance. Using continuous accelerometry, subjects with MS spent less time in moderate-to-vigorous physical activity compared to controls (20.4 minutes/day vs 35.4 minutes/day, p=0.0003). The POMS cohort reported significantly higher levels of depression and fatigue, but self-reported similar levels of daily physical activity as controls. CONCLUSIONS: Youth with POMS exhibit slower 6MW performance and less daily engagement in moderate-to-vigorous physical activity, suggesting limitations in functional walking capacity, endurance, and daily activity behavior. Limitations in walking endurance and capacity are most prominent in those youth who are overweight/obese and living with MS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, compared to healthy controls, patients with pediatric-onset MS walk shorter distances on the 6 minute walk test, are less able to accelerate to peak speed at the end of the test, and are less physically active.

Body size perceptions & diet modification in youth with multiple sclerosis.

BACKGROUND: Investigate the perceptions of pediatric multiple sclerosis (MS) patients regarding their body size and assess the feasibility of recruitment for a study of diet modification in this unique population. METHODS: This cross-sectional study surveyed a cohort of 43 consecutive youth with MS. The survey queried participant demographics, clinical disease characteristics, body size perception, and opinions of diet modification RESULTS: : While over three quarters of surveyed participants were overweight/obese, 58% of these participants did not self-identify as such. A single participant was attempting a diet at the time of survey, but 88% of participants indicated interest in pursuing diet modification. BMI category did not impact an individual's willingness to pursue diet intervention; however, obese participants were more willing to participate in diet intervention for longer durations. CONCLUSION: A significant proportion of MS youth have an elevated BMI, yet the majority have the self-perception that they are not overweight or obese. Regardless of BMI, most youth with MS have an interest in pursuing diet modification in attempts to benefit their disease course.

The Multiple Sclerosis Functional Composite and Symbol Digit Modalities Test as outcome measures in pediatric multiple sclerosis.

BACKGROUND: There is an increasing number of pediatric multiple sclerosis (MS) clinical trials occurring; however, data validating outcome metrics that accurately capture functional disability within pediatric cohorts are limited. OBJECTIVE: The aim of this study was to investigate the ability of the MS Functional Composite (MSFC) and Symbol Digit Modalities Test (SDMT) to distinguish functional disability in pediatric MS patients. METHODS: A total of 20 pediatric MS patients and 40 age and sex-matched controls completed the SDMT and MSFC components: a timed 25-foot walk (T25FW); 9-hole peg test (9HPT); and paced auditory serial addition test (PASAT). Z scores for MS patients were created for each test based on control means. MS patients underwent Expanded Disability Status Scale (EDSS) examination. RESULTS: Pediatric MS patients exhibited low levels of disability on EDSS, median [range]: 1.5 [1.0-3.0]. Compared with controls, MS patients performed significantly lower on SDMT (p = 0.0002) and all MSFC components: T25FW (p = 0.001), 9HPT (p = 0.01), and PASAT (p = 0.004). SDMT and MSFC performance were not correlated with EDSS. CONCLUSIONS: Despite low levels of neurologic disability as measured by EDSS, pediatric patients with MS exhibit impaired performance in leg function, upper limb fine motor function, and auditory/visuospatial processing speeds, supporting the value of the MSFC and SDMT in this population. Longitudinal studies are needed to further validate their utility.