Disease-specific wearable sensor algorithms for profiling activity, gait, and balance in individuals with Charcot-Marie-Tooth disease type 1A.

BACKGROUND/AIMS: Charcot-Marie-Tooth Disease type 1A (CMT1A), the most common inherited peripheral neuropathy, is characterized by progressive sensory loss and weakness, which results in impaired mobility. Increased understanding of the genetics and pathophysiology of CMT1A has led to development of potential therapeutic agents, necessitating clinical trial readiness. Wearable sensors may provide useful outcome measures for future trials. METHODS: Individuals with CMT1A and unaffected controls were recruited for this 12-month study. Participants wore sensors for in-clinic assessments and at-home, from which activity, gait, and balance metrics were derived. Mann-Whitney U tests were used to analyze group differences for activity, gait, and balance parameters. Test-retest reliability of gait and balance parameters and correlations of these parameters with clinical outcome assessments (COAs) were examined. RESULTS: Thirty individuals, 15 CMT1A, and 15 controls, participated. Gait and balance metrics demonstrated moderate to excellent reliability. CMT1A participants had longer step durations (p < .001), shorter step lengths (p = .03), slower gait speeds (p < .001), and greater postural sway (p < .001) than healthy controls. Moderate correlations were found between CMT-Functional Outcome Measure and step length (r = -0.59; p = .02), and gait speed (r = 0.64; p = .01); 11 out of 15 CMT1A participants demonstrated significant increases in stride duration between the first and last quarter of the 6-min walk test, suggesting fatigue. INTERPRETATION: In this initial study, gait and balance metrics derived from wearable sensors were reliable and associated with COAs in individuals with CMT1A. Larger longitudinal studies are needed to confirm our findings and evaluate sensitivity and utility of these disease-specific algorithms for clinical trial use.

Management and outcome of vagus nerve stimulator implantation: experience of an otolaryngeal/neuropediatric cooperation.

OBJECTIVE: Vagus nerve stimulator (VNS) implantation is an established therapy for pharmacoresistant epilepsy that is not amenable to curative epilepsy surgery. Historically, VNS implantation has been performed by neurosurgeons, but otolaryngologist involvement is increasingly common. In this retrospective study, we aimed to evaluate the efficacy and safety of VNS implantation in children and adolescents from the otolaryngologists' perspective. METHODS: This study included children and adolescents who had undergone VNS implantation at the study center between 2014 and 2018. Patient files were analyzed with regards to the durations of device implantation and hospitalization, postoperative complications, and clinical outcome, including seizure frequency, clinical global impression of improvement (CGI-I) score, and quality of life (QoL). RESULTS: A total of 73 children underwent VNS surgery. The median age at implantation was 9.3 ± 4.6 years, and median epilepsy duration before VNS surgery was 6 ± 4 years. Lennox-Gastaut syndrome was the most common syndrome diagnosis (62.3%), and structural abnormalities (49.3%) the most frequent etiology. Operation times ranged from 30 to 200 min, and median postoperative hospitalization length was 2 ± 0.9 days. No complications occurred, except for four revisions and two explantations due to local infections (2.7%). Among our patients, 76.7% were responders (≥ 50% reduction in seizure frequency), 72.1% showed improved CGI-I scores, and 18.6-60.5% exhibited considerable improvements in the QoL categories energy, emotional health, and cognitive functions. CONCLUSION: Our results indicate that VNS implantation is a highly effective and safe treatment option for children and adolescents with AED-refractory epilepsies who are not candidates for curative epilepsy surgery.

Reliability and validity of the FSHD-composite outcome measure in childhood facioscapulohumeral dystrophy.

This study aims to investigate intra-rater reliability and construct validity of the Facioscapulohumeral Dystrophy Composite Outcome Measure (FSHD-COM), in childhood FSHD. Participants included eighteen children with FSHD, and matched healthy controls. Reliability data were collected from 15 participants with FSHD over two testing sessions. Validity data were collected from all participants. Participants with FSHD completed; the FSHD-COM (and modified pediatric version), Motor Function Measure-32 (MFM-32), FSHD Severity Scales, Performance of the Upper Limb 2.0, Pediatric Quality of Life™ Neuromuscular Module and pediatric FSHD Health-Index Questionnaire. Both versions of the FSHD-COM showed excellent intra-rater reliability (ICC1,2 > 0.99, lower 95%CI > 0.98) with a Minimal Detectable Change (MDC95%) of ≤14.5%. The FSHD-COM had robust and widespread correlations with other related outcome measures. The FSHD-COM versions and 6 min walk test effectively discriminated between children with and without FSHD; the MFM-32 and 10 m walk/run test did not. Ceiling effects were not observed on either version of the FSHD-COM. Reliability and validity findings in this childhood FSHD study concord with estimates in adults. Both versions of the FSHD-COM were effective in discriminating disease in children with mild FSHD symptoms. The FSHD-COM has the potential to be a useful measure of function across the life span.

Urinary dopamine sulfate: regulations and significance in neurological disorders.

Dopamine-3-O-sulfate (DA-3-O-S) and dopamine-4-O-sulfate (DA-4-O-S) are important end products of L-dopa metabolism. Therefore they may give indications of disturbances in the peripheral metabolism of catecholamines, when measured in urine samples of patients with Parkinson's disease (PD). In addition, information about the reliability of DA sulfatation after L-dopa therapy may be of significance for its role in the elimination of DA from the peripheral nervous system. Although DA-3-O-S appears to be the predominant sulfo-conjugate in urine, there are no changes in PD nor in depression syndrome compared to controls with or without other neurological disorders. By contrast, DA-4-O-S is significantly decreased in de novo PD subjects. However, a similar reduction is notable in patients with other neurological disorders. In depressed persons the loss of this compound was less pronounced as compared to de novo PD. Treatment with combined L-dopa therapy caused increased excretion of DA-3-O-S, while changes in DA-4-O-S were only marginal. It is concluded that urinary DA-3-O-S cannot be used as marker for PD, while DA-4-O-S is significantly reduced in a variety of neurological disorders and in particular in de novo PD. Further studies are necessary to elucidate its role as possible peripheral marker to distinguish preclinical PD and depression syndrome.

Preparation of dopamine 3-O-sulphate and dopamine 4-O-sulphate as reference substances and high-performance liquid chromatographic trace determination.

Simple syntheses of the biologically important but hitherto difficult to obtain dopamine sulpho conjugates dopamine 3-O-sulphate (I) and dopamine 4-O-sulphate (II), as analytical reference substances, starting from dopamine hydrochloride are described. A method for the determination of I and II with reversed-phase high-performance liquid chromatographic separation and coulometric detection in human urine together with calibration and current-voltage curves are presented. Detection limits of approximately 100 pg of I or II and unequivocal substance identifications even in very complex substrates such as human urine are reported.

A study of brain dopamine sulfate levels in relation to free dopamine and homovanillic acid in Parkinson's disease.

High performance liquid chromatography with electrochemical detection was used for determining dopamine sulfate in human brain tissues. Dopamine sulfate was examined in the striatum and frontal cortex of human brain. The concentrations of dopamine sulfate in these regions are extremely low in comparison to free dopamine, and to dopamine sulfoconjugates in the cerebrospinal fluid, plasma and urine. Data obtained with this technique in human post mortem brain specimens indicate that the analysis of tissues and body fluids for dopamine conjugates is useful for profiling metabolic dopamine activity in controls and neurodegenerative disorders like Parkinson's disease.

Active immunization against varicella of children with acute leukaemia or other malignancies on maintenance chemotherapy.

Twenty-six patients with acute leukaemia and other malignancies susceptible to varicella were vaccinated with the Oka-strain live attenuated varicella vaccine during maintenance chemotherapy. All recipients showed no adverse clinical reactions. There was no spread of vaccine virus. Seroconversion was 94% in seronegative patients. Among those having low antibody titres before vaccination, a booster effect was demonstrable in 56%. None of the seroconverted recipients contracted varicella despite documented contact exposure. No case of herpes zoster occurred. The results suggest that, in immunocompromised children, live varicella vaccination has a protective effect against varicella infection which may result in a mortality rate of up to 7% in these patients.

[Active chickenpox vaccination of children with acute leukemia or other neoplastic diseases]. / Aktive Varizellenimpfung bei Kindern mit akuter Leukämie oder anderen neoplastischen Erkrankungen.

26 patients with acute leukemia and other malignancies susceptible to varicella were vaccinated during maintenance chemotherapy. Vaccination was done with OKA strain of live attenuated varicella vaccine developed by Takahashi 1974. All recipients showed no adverse clinical reactions. There was no spread of vaccine virus to others. Seroconversion was 94% in seronegative patients. In those having low antibody titers before vaccination in 56% booster effect was demonstrable. None of the seroconverted recipients contracted varicella in spite of documented contact exposure. Vaccine zoster was not observed. The results suggest that in immunocompromised children live varicella vaccination has a protective effect against varicella infection which has a described mortality rate up 7% in this patients.